Hypertension

At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.

While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.

Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.

“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.

That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.

In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.

In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.

This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.

As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
 

Ask Early, Ask Often

Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.

It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.

Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:

• Are you having trouble with erections or having sex?
• Are you getting up at night to pass urine more than once?

“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”

Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”

Addressing the Issue

Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.

Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”

“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.

Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.

Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
 

A version of this article appeared on Medscape.com.

At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.

While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.

Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.

“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.

That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.

In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.

In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.

This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.

As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
 

Ask Early, Ask Often

Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.

It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.

Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:

• Are you having trouble with erections or having sex?
• Are you getting up at night to pass urine more than once?

“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”

Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”

Addressing the Issue

Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.

Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”

“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.

Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.

Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
 

A version of this article appeared on Medscape.com.

At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.

While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.

Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.

“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.

That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.

In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.

In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.

This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.

As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
 

Ask Early, Ask Often

Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.

It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.

Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:

• Are you having trouble with erections or having sex?
• Are you getting up at night to pass urine more than once?

“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”

Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”

Addressing the Issue

Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.

Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”

“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.

Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.

Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — Updated guidelines for the management of atrial fibrillation released by the European Society of Cardiology are revamping the approach to care for this complex, multifactorial disease.

The identification and treatment of comorbidities and risk factors are the initial and central components of patient management, and are crucial for all other aspects of care for patients with atrial fibrillation (AF), Isabelle Van Gelder, MD, PhD, professor of cardiology at the University Medical Center in Groningen, the Netherlands, explained at the European Society of Cardiology (ESC) Congress.

It is not just appropriate to place the same emphasis on the control of comorbidities as on the rhythm disturbance, it is critical, said Dr. Van Gelder, who served as chair of the ESC-AF guidelines task force.

Comorbidities are the drivers of both the onset and recurrence of atrial fibrillation, and a dynamic approach to comorbidities is “central for the success of AF management.”
 

Class I Recommendation

In fact, on the basis of overwhelming evidence, a class I recommendation has been issued for a large number of goals in the comorbidity and risk factor management step of atrial fibrillation management, including those for hypertension, components of heart failure, obesity, diabetes, alcohol consumption, and exercise.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors “should be offered to all patients with AF,” according to Dr. Van Gelder, who identified this as a new class I recommendation.

Patients who are not managed aggressively for the listed comorbidities ultimately face “treatment failure, poor patient outcomes, and a waste of healthcare resources,” she said.

Control of sleep apnea is also noted as a key target, although Van Gelder acknowledged that the supporting evidence only allows for a class IIb recommendation.

Control of comorbidities is not a new idea. In the 2023 joint guideline, led by a consortium of professional groups, including the American Heart Association (AHA) and the American College of Cardiology (ACC), the control of comorbidities, including most of those identified in the new ESC guidelines, was second in a list of 10 key take-home messages.

However, the new ESC guidelines have prioritized comorbidity management by listing it first in each of the specific patient-care pathways developed to define optimized care. 

These pathways, defined in algorithms for newly diagnosed AF, paroxysmal AF, and persistent AF, always start with the assessment of comorbidities, followed by step A — avoiding stroke — largely with anticoagulation.

Direct oral anticoagulants should be used, “except in those with a mechanical valve or mitral stenosis,” Dr. Van Gelder said. This includes, essentially, all patients with a CHA2DS2-VASc score of 2 or greater, and it should be “considered” in those with a score of 1. 

The ESC framework has been identified with the acronym AF-CARE, in which the C stands for comorbidities.

In the A step of the framework, identifying and treating all modifiable bleeding risk factors in AF patients is a class I recommendation. On the basis of a class III recommendation, she cautioned against withholding anticoagulants because of CHA2DS2-VASc risk factors alone. Rather, Dr. Van Gelder called the decision to administer or withhold anticoagulation — like all decisions — one that should be individualized in consultation with the patient.

For reducing AF symptoms and rhythm control, the specific pathways diverge for newly diagnosed AF, paroxysmal AF, and persistent AF. Like all of the guidelines, the specific options for symptom management and AF ablation are color coded, with green signifying level 1 evidence.

The evaluation and dynamic reassessment step refers to the need to periodically assess patients for new modifiable risk factors related to comorbidities, risk for stroke, risk for bleeding, and risk for AF. 

The management of risk factors for AF has long been emphasized in guidelines, but a previous focus on AF with attention to comorbidities has been replaced by a focus on comorbidities with an expectation of more durable AF control. The success of this pivot is based on multidisciplinary care, chosen in collaboration with the patient, to reduce or eliminate the triggers of AF and the risks of its complications.
 

Pathways Are Appropriate for All Patients

A very important recommendation — and this is new — is “to treat all our patients with atrial fibrillation, whether they are young or old, men or women, Black or White, or at high or low risk, according to our patient-centered integrated AF-CARE approach,” Dr. Van Gelder said.

The changes reflect a shared appreciation for the tight relation between the control of comorbidities and the control of AF, according to José A. Joglar, MD, professor of cardiac electrophysiologic research at the University of Texas Southwestern Medical Center in Dallas. Dr. Joglar was chair of the writing committee for the joint 2023 AF guidelines released by the AHA, ACC, the American College of Clinical Pharmacy, and the Heart Rhythm Society.

“It is increasingly clear that AF in many cases is the consequence of underlying risk factors and comorbidities, which cannot be separated from AF alone,” Dr. Joglar explained in an interview.

This was placed first “to emphasize the importance of viewing AFib as a complex disease that requires a holistic, multidisciplinary approach to care, as opposed to being viewed just as a rhythm abnormality,” he said.
 

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

LONDON — Updated guidelines for the management of atrial fibrillation released by the European Society of Cardiology are revamping the approach to care for this complex, multifactorial disease.

The identification and treatment of comorbidities and risk factors are the initial and central components of patient management, and are crucial for all other aspects of care for patients with atrial fibrillation (AF), Isabelle Van Gelder, MD, PhD, professor of cardiology at the University Medical Center in Groningen, the Netherlands, explained at the European Society of Cardiology (ESC) Congress.

It is not just appropriate to place the same emphasis on the control of comorbidities as on the rhythm disturbance, it is critical, said Dr. Van Gelder, who served as chair of the ESC-AF guidelines task force.

Comorbidities are the drivers of both the onset and recurrence of atrial fibrillation, and a dynamic approach to comorbidities is “central for the success of AF management.”
 

Class I Recommendation

In fact, on the basis of overwhelming evidence, a class I recommendation has been issued for a large number of goals in the comorbidity and risk factor management step of atrial fibrillation management, including those for hypertension, components of heart failure, obesity, diabetes, alcohol consumption, and exercise.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors “should be offered to all patients with AF,” according to Dr. Van Gelder, who identified this as a new class I recommendation.

Patients who are not managed aggressively for the listed comorbidities ultimately face “treatment failure, poor patient outcomes, and a waste of healthcare resources,” she said.

Control of sleep apnea is also noted as a key target, although Van Gelder acknowledged that the supporting evidence only allows for a class IIb recommendation.

Control of comorbidities is not a new idea. In the 2023 joint guideline, led by a consortium of professional groups, including the American Heart Association (AHA) and the American College of Cardiology (ACC), the control of comorbidities, including most of those identified in the new ESC guidelines, was second in a list of 10 key take-home messages.

However, the new ESC guidelines have prioritized comorbidity management by listing it first in each of the specific patient-care pathways developed to define optimized care. 

These pathways, defined in algorithms for newly diagnosed AF, paroxysmal AF, and persistent AF, always start with the assessment of comorbidities, followed by step A — avoiding stroke — largely with anticoagulation.

Direct oral anticoagulants should be used, “except in those with a mechanical valve or mitral stenosis,” Dr. Van Gelder said. This includes, essentially, all patients with a CHA2DS2-VASc score of 2 or greater, and it should be “considered” in those with a score of 1. 

The ESC framework has been identified with the acronym AF-CARE, in which the C stands for comorbidities.

In the A step of the framework, identifying and treating all modifiable bleeding risk factors in AF patients is a class I recommendation. On the basis of a class III recommendation, she cautioned against withholding anticoagulants because of CHA2DS2-VASc risk factors alone. Rather, Dr. Van Gelder called the decision to administer or withhold anticoagulation — like all decisions — one that should be individualized in consultation with the patient.

For reducing AF symptoms and rhythm control, the specific pathways diverge for newly diagnosed AF, paroxysmal AF, and persistent AF. Like all of the guidelines, the specific options for symptom management and AF ablation are color coded, with green signifying level 1 evidence.

The evaluation and dynamic reassessment step refers to the need to periodically assess patients for new modifiable risk factors related to comorbidities, risk for stroke, risk for bleeding, and risk for AF. 

The management of risk factors for AF has long been emphasized in guidelines, but a previous focus on AF with attention to comorbidities has been replaced by a focus on comorbidities with an expectation of more durable AF control. The success of this pivot is based on multidisciplinary care, chosen in collaboration with the patient, to reduce or eliminate the triggers of AF and the risks of its complications.
 

Pathways Are Appropriate for All Patients

A very important recommendation — and this is new — is “to treat all our patients with atrial fibrillation, whether they are young or old, men or women, Black or White, or at high or low risk, according to our patient-centered integrated AF-CARE approach,” Dr. Van Gelder said.

The changes reflect a shared appreciation for the tight relation between the control of comorbidities and the control of AF, according to José A. Joglar, MD, professor of cardiac electrophysiologic research at the University of Texas Southwestern Medical Center in Dallas. Dr. Joglar was chair of the writing committee for the joint 2023 AF guidelines released by the AHA, ACC, the American College of Clinical Pharmacy, and the Heart Rhythm Society.

“It is increasingly clear that AF in many cases is the consequence of underlying risk factors and comorbidities, which cannot be separated from AF alone,” Dr. Joglar explained in an interview.

This was placed first “to emphasize the importance of viewing AFib as a complex disease that requires a holistic, multidisciplinary approach to care, as opposed to being viewed just as a rhythm abnormality,” he said.
 

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

LONDON — Updated guidelines for the management of atrial fibrillation released by the European Society of Cardiology are revamping the approach to care for this complex, multifactorial disease.

The identification and treatment of comorbidities and risk factors are the initial and central components of patient management, and are crucial for all other aspects of care for patients with atrial fibrillation (AF), Isabelle Van Gelder, MD, PhD, professor of cardiology at the University Medical Center in Groningen, the Netherlands, explained at the European Society of Cardiology (ESC) Congress.

It is not just appropriate to place the same emphasis on the control of comorbidities as on the rhythm disturbance, it is critical, said Dr. Van Gelder, who served as chair of the ESC-AF guidelines task force.

Comorbidities are the drivers of both the onset and recurrence of atrial fibrillation, and a dynamic approach to comorbidities is “central for the success of AF management.”
 

Class I Recommendation

In fact, on the basis of overwhelming evidence, a class I recommendation has been issued for a large number of goals in the comorbidity and risk factor management step of atrial fibrillation management, including those for hypertension, components of heart failure, obesity, diabetes, alcohol consumption, and exercise.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors “should be offered to all patients with AF,” according to Dr. Van Gelder, who identified this as a new class I recommendation.

Patients who are not managed aggressively for the listed comorbidities ultimately face “treatment failure, poor patient outcomes, and a waste of healthcare resources,” she said.

Control of sleep apnea is also noted as a key target, although Van Gelder acknowledged that the supporting evidence only allows for a class IIb recommendation.

Control of comorbidities is not a new idea. In the 2023 joint guideline, led by a consortium of professional groups, including the American Heart Association (AHA) and the American College of Cardiology (ACC), the control of comorbidities, including most of those identified in the new ESC guidelines, was second in a list of 10 key take-home messages.

However, the new ESC guidelines have prioritized comorbidity management by listing it first in each of the specific patient-care pathways developed to define optimized care. 

These pathways, defined in algorithms for newly diagnosed AF, paroxysmal AF, and persistent AF, always start with the assessment of comorbidities, followed by step A — avoiding stroke — largely with anticoagulation.

Direct oral anticoagulants should be used, “except in those with a mechanical valve or mitral stenosis,” Dr. Van Gelder said. This includes, essentially, all patients with a CHA2DS2-VASc score of 2 or greater, and it should be “considered” in those with a score of 1. 

The ESC framework has been identified with the acronym AF-CARE, in which the C stands for comorbidities.

In the A step of the framework, identifying and treating all modifiable bleeding risk factors in AF patients is a class I recommendation. On the basis of a class III recommendation, she cautioned against withholding anticoagulants because of CHA2DS2-VASc risk factors alone. Rather, Dr. Van Gelder called the decision to administer or withhold anticoagulation — like all decisions — one that should be individualized in consultation with the patient.

For reducing AF symptoms and rhythm control, the specific pathways diverge for newly diagnosed AF, paroxysmal AF, and persistent AF. Like all of the guidelines, the specific options for symptom management and AF ablation are color coded, with green signifying level 1 evidence.

The evaluation and dynamic reassessment step refers to the need to periodically assess patients for new modifiable risk factors related to comorbidities, risk for stroke, risk for bleeding, and risk for AF. 

The management of risk factors for AF has long been emphasized in guidelines, but a previous focus on AF with attention to comorbidities has been replaced by a focus on comorbidities with an expectation of more durable AF control. The success of this pivot is based on multidisciplinary care, chosen in collaboration with the patient, to reduce or eliminate the triggers of AF and the risks of its complications.
 

Pathways Are Appropriate for All Patients

A very important recommendation — and this is new — is “to treat all our patients with atrial fibrillation, whether they are young or old, men or women, Black or White, or at high or low risk, according to our patient-centered integrated AF-CARE approach,” Dr. Van Gelder said.

The changes reflect a shared appreciation for the tight relation between the control of comorbidities and the control of AF, according to José A. Joglar, MD, professor of cardiac electrophysiologic research at the University of Texas Southwestern Medical Center in Dallas. Dr. Joglar was chair of the writing committee for the joint 2023 AF guidelines released by the AHA, ACC, the American College of Clinical Pharmacy, and the Heart Rhythm Society.

“It is increasingly clear that AF in many cases is the consequence of underlying risk factors and comorbidities, which cannot be separated from AF alone,” Dr. Joglar explained in an interview.

This was placed first “to emphasize the importance of viewing AFib as a complex disease that requires a holistic, multidisciplinary approach to care, as opposed to being viewed just as a rhythm abnormality,” he said.
 

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

LONDON — Simplified and more aggressive targets are among the significant changes to the updated hypertension guidelines released by the European Society of Cardiology.

For most treated patients, the new systolic blood pressure goal is a target of 120 mm Hg to 129 mm Hg, which is a move away from the previous two-step recommendation.

Although the updated guidelines, presented here at the ESC Congress, continue to define hypertension as a systolic BP of at least 140 mm Hg and a diastolic BP of at least 90 mm Hg, there is a new category — elevated BP. This is defined as a systolic BP of 120 mm Hg to 139 mm Hg or a diastolic BP of 70 mm Hg to 89 mm Hg, and cardiovascular risk assessment is advised to guide treatment, particularly in patients with a BP of at least 130/80 mm Hg.

The guidelines also introduce new recommendations for lifestyle options to help lower BP, including changes to exercise advice and the addition of potassium supplementation. And for the first time, the ESC guidelines provide recommendations for the use of renal denervation to treat hypertension in certain circumstances.

The guidelines were produced by an international panel, led by Bill McEvoy, MB BCh, from the University of Galway, Ireland, and Rhian Touyz, MB BCh, PhD, from McGill University in Montreal.
 

Three Categories of Blood Pressure

There are now three categories for BP classification — non-elevated (< 120/70 mm Hg), elevated (120 mm Hg to139 mm Hg/70 mm Hg to 89 mm Hg), and hypertension (≥ 140/90 mm Hg) — Dr. McEvoy reported during a session on the new guidelines here at ESC.

The emphasis on out-of-office BP measurement is stronger than in previous guidelines, but office measurement will still be used, he said.

All patients in the hypertension category qualify for treatment, whereas those in the new elevated BP category will be subject to cardiovascular risk stratification before a treatment decision is made.

Patients in the elevated BP category who also have moderate or severe chronic kidney disease, established cardiovascular disease, diabetes, or familial hypercholesterolemia are among those considered at increased risk for cardiovascular disease, as are patients with an estimated 10-year cardiovascular risk of 10% or higher. In such patients with a confirmed BP of at least 130/80 mm Hg, after 3 months of lifestyle intervention, pharmacologic treatment is recommended.

“This new category of elevated blood pressure recognizes that people do not go from normal blood pressure to hypertensive overnight,” Dr. McEvoy said. “It is, in most cases, a steady gradient of change, and different subgroups of patients — for example, those at a higher risk of developing cardiovascular disease — could benefit from more intensive treatment before their blood pressure reaches the traditional threshold of hypertension.”
 

New Lower Target

The major change in target pressures in these guidelines is based on new clinical trial data that confirm that lower pressures lead to lower cardiovascular event rates, resulting in the new systolic BP target of 120 mm Hg to 129 mm Hg for most patients receiving antihypertensive medications.

This systolic target represents a major change from previous European guidelines, Dr. McEvoy said, which have generally recommended that patients be treated to a target of less than 140/90 mm Hg and, only after that has been reached, then treated to a target of less than 130/80 mm Hg (a two-step approach).

“This change is driven by new trial evidence confirming that more intensive blood pressure treatment targets reduce cardiovascular outcomes across a broad spectrum of eligible patients,” Dr. McEvoy said.

There are, however, several caveats to this recommendation, including the requirement that treatment to this target be well tolerated; more lenient targets can be considered in people with symptomatic orthostatic hypotension, those 85 years and older, and those with moderate to severe frailty or a limited life expectancy. For these patients, the guidelines recommend a target “that is as low as reasonably achievable.”
 

More in Line With US Guidelines

The new European guidelines are now more in line with the American guidelines, said Eugene Yang, MD, from the University of Washington in Seattle, who is chair of the Hypertension Writing Group at the American College of Cardiology.

“These new European guidelines have thoughtfully used the latest study data to simplify recommendations for a specific lower blood pressure target. This is a step forward. There is now a greater alignment of European and US guidelines. This is good to reduce confusion and build consensus across the world,” he said.

Both sets of guidelines now recommend a BP target of less than 130/80 mm Hg for most people. 

“I think the Europeans have now embraced this more aggressive target because there are many more studies now showing that these lower blood pressure levels do lead to a reduction in cardiovascular events,” Dr. Yang explained. “When the last European guidelines came out, there was only SPRINT. Now there are several more studies showing similar results.”
 

New Lifestyle Advice

The updated recommendation of 75 minutes of vigorous-intensity aerobic exercise per week has been added as an alternative to the previous recommendation of at least 2.5 hours per week of moderate-intensity aerobic exercise. This should be complemented with low- or moderate-intensity dynamic or isometric resistance training two to three times a week. 

It is also recommended that people with hypertension, but without moderate or advanced chronic kidney disease, increase potassium intake with salt substitutes or diets rich in fruits and vegetables.
 

Renal Denervation Included for First Time 

For the first time, the guidelines include the option of renal denervation for the treatment of hypertension — at medium- to high-volume centers — for patients with resistant hypertension that is uncontrolled despite a three-drug combination.

However, renal denervation is not recommended as a first-line treatment because of the lack of evidence of a benefit in cardiovascular outcomes. It is also not recommended for patients with highly impaired renal function or secondary causes of hypertension.

Dr. Yang said he approves of the inclusion of a frailty assessment in the new guidelines and less aggressive targets for people who are in poor health and older than age 85 years, but added that, “on the whole, they have less age-specific stratification than before, which is a significant change, and a good one in my view.” 

Again, this is like the American guidelines, which have no age cutoffs and a target of less than 130/80 mm Hg for all, with the caveat that clinical judgment may be needed for individuals who are institutionalized, he added.

Dr. Yang said he was not as keen on the requirement for a cardiovascular risk assessment to guide treatment decisions for people with a systolic BP in the 130 mm Hg to 139 mm Hg range, although this is also included in the current American guidelines.

“As a clinician, I think this complicates things a bit too much and, as such, will be a barrier to treatment. In my view, blood pressure treatment recommendations need to be as simple as possible, so I think we still have some work to do there,” he said.

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

LONDON — Simplified and more aggressive targets are among the significant changes to the updated hypertension guidelines released by the European Society of Cardiology.

For most treated patients, the new systolic blood pressure goal is a target of 120 mm Hg to 129 mm Hg, which is a move away from the previous two-step recommendation.

Although the updated guidelines, presented here at the ESC Congress, continue to define hypertension as a systolic BP of at least 140 mm Hg and a diastolic BP of at least 90 mm Hg, there is a new category — elevated BP. This is defined as a systolic BP of 120 mm Hg to 139 mm Hg or a diastolic BP of 70 mm Hg to 89 mm Hg, and cardiovascular risk assessment is advised to guide treatment, particularly in patients with a BP of at least 130/80 mm Hg.

The guidelines also introduce new recommendations for lifestyle options to help lower BP, including changes to exercise advice and the addition of potassium supplementation. And for the first time, the ESC guidelines provide recommendations for the use of renal denervation to treat hypertension in certain circumstances.

The guidelines were produced by an international panel, led by Bill McEvoy, MB BCh, from the University of Galway, Ireland, and Rhian Touyz, MB BCh, PhD, from McGill University in Montreal.
 

Three Categories of Blood Pressure

There are now three categories for BP classification — non-elevated (< 120/70 mm Hg), elevated (120 mm Hg to139 mm Hg/70 mm Hg to 89 mm Hg), and hypertension (≥ 140/90 mm Hg) — Dr. McEvoy reported during a session on the new guidelines here at ESC.

The emphasis on out-of-office BP measurement is stronger than in previous guidelines, but office measurement will still be used, he said.

All patients in the hypertension category qualify for treatment, whereas those in the new elevated BP category will be subject to cardiovascular risk stratification before a treatment decision is made.

Patients in the elevated BP category who also have moderate or severe chronic kidney disease, established cardiovascular disease, diabetes, or familial hypercholesterolemia are among those considered at increased risk for cardiovascular disease, as are patients with an estimated 10-year cardiovascular risk of 10% or higher. In such patients with a confirmed BP of at least 130/80 mm Hg, after 3 months of lifestyle intervention, pharmacologic treatment is recommended.

“This new category of elevated blood pressure recognizes that people do not go from normal blood pressure to hypertensive overnight,” Dr. McEvoy said. “It is, in most cases, a steady gradient of change, and different subgroups of patients — for example, those at a higher risk of developing cardiovascular disease — could benefit from more intensive treatment before their blood pressure reaches the traditional threshold of hypertension.”
 

New Lower Target

The major change in target pressures in these guidelines is based on new clinical trial data that confirm that lower pressures lead to lower cardiovascular event rates, resulting in the new systolic BP target of 120 mm Hg to 129 mm Hg for most patients receiving antihypertensive medications.

This systolic target represents a major change from previous European guidelines, Dr. McEvoy said, which have generally recommended that patients be treated to a target of less than 140/90 mm Hg and, only after that has been reached, then treated to a target of less than 130/80 mm Hg (a two-step approach).

“This change is driven by new trial evidence confirming that more intensive blood pressure treatment targets reduce cardiovascular outcomes across a broad spectrum of eligible patients,” Dr. McEvoy said.

There are, however, several caveats to this recommendation, including the requirement that treatment to this target be well tolerated; more lenient targets can be considered in people with symptomatic orthostatic hypotension, those 85 years and older, and those with moderate to severe frailty or a limited life expectancy. For these patients, the guidelines recommend a target “that is as low as reasonably achievable.”
 

More in Line With US Guidelines

The new European guidelines are now more in line with the American guidelines, said Eugene Yang, MD, from the University of Washington in Seattle, who is chair of the Hypertension Writing Group at the American College of Cardiology.

“These new European guidelines have thoughtfully used the latest study data to simplify recommendations for a specific lower blood pressure target. This is a step forward. There is now a greater alignment of European and US guidelines. This is good to reduce confusion and build consensus across the world,” he said.

Both sets of guidelines now recommend a BP target of less than 130/80 mm Hg for most people. 

“I think the Europeans have now embraced this more aggressive target because there are many more studies now showing that these lower blood pressure levels do lead to a reduction in cardiovascular events,” Dr. Yang explained. “When the last European guidelines came out, there was only SPRINT. Now there are several more studies showing similar results.”
 

New Lifestyle Advice

The updated recommendation of 75 minutes of vigorous-intensity aerobic exercise per week has been added as an alternative to the previous recommendation of at least 2.5 hours per week of moderate-intensity aerobic exercise. This should be complemented with low- or moderate-intensity dynamic or isometric resistance training two to three times a week. 

It is also recommended that people with hypertension, but without moderate or advanced chronic kidney disease, increase potassium intake with salt substitutes or diets rich in fruits and vegetables.
 

Renal Denervation Included for First Time 

For the first time, the guidelines include the option of renal denervation for the treatment of hypertension — at medium- to high-volume centers — for patients with resistant hypertension that is uncontrolled despite a three-drug combination.

However, renal denervation is not recommended as a first-line treatment because of the lack of evidence of a benefit in cardiovascular outcomes. It is also not recommended for patients with highly impaired renal function or secondary causes of hypertension.

Dr. Yang said he approves of the inclusion of a frailty assessment in the new guidelines and less aggressive targets for people who are in poor health and older than age 85 years, but added that, “on the whole, they have less age-specific stratification than before, which is a significant change, and a good one in my view.” 

Again, this is like the American guidelines, which have no age cutoffs and a target of less than 130/80 mm Hg for all, with the caveat that clinical judgment may be needed for individuals who are institutionalized, he added.

Dr. Yang said he was not as keen on the requirement for a cardiovascular risk assessment to guide treatment decisions for people with a systolic BP in the 130 mm Hg to 139 mm Hg range, although this is also included in the current American guidelines.

“As a clinician, I think this complicates things a bit too much and, as such, will be a barrier to treatment. In my view, blood pressure treatment recommendations need to be as simple as possible, so I think we still have some work to do there,” he said.

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

LONDON — Simplified and more aggressive targets are among the significant changes to the updated hypertension guidelines released by the European Society of Cardiology.

For most treated patients, the new systolic blood pressure goal is a target of 120 mm Hg to 129 mm Hg, which is a move away from the previous two-step recommendation.

Although the updated guidelines, presented here at the ESC Congress, continue to define hypertension as a systolic BP of at least 140 mm Hg and a diastolic BP of at least 90 mm Hg, there is a new category — elevated BP. This is defined as a systolic BP of 120 mm Hg to 139 mm Hg or a diastolic BP of 70 mm Hg to 89 mm Hg, and cardiovascular risk assessment is advised to guide treatment, particularly in patients with a BP of at least 130/80 mm Hg.

The guidelines also introduce new recommendations for lifestyle options to help lower BP, including changes to exercise advice and the addition of potassium supplementation. And for the first time, the ESC guidelines provide recommendations for the use of renal denervation to treat hypertension in certain circumstances.

The guidelines were produced by an international panel, led by Bill McEvoy, MB BCh, from the University of Galway, Ireland, and Rhian Touyz, MB BCh, PhD, from McGill University in Montreal.
 

Three Categories of Blood Pressure

There are now three categories for BP classification — non-elevated (< 120/70 mm Hg), elevated (120 mm Hg to139 mm Hg/70 mm Hg to 89 mm Hg), and hypertension (≥ 140/90 mm Hg) — Dr. McEvoy reported during a session on the new guidelines here at ESC.

The emphasis on out-of-office BP measurement is stronger than in previous guidelines, but office measurement will still be used, he said.

All patients in the hypertension category qualify for treatment, whereas those in the new elevated BP category will be subject to cardiovascular risk stratification before a treatment decision is made.

Patients in the elevated BP category who also have moderate or severe chronic kidney disease, established cardiovascular disease, diabetes, or familial hypercholesterolemia are among those considered at increased risk for cardiovascular disease, as are patients with an estimated 10-year cardiovascular risk of 10% or higher. In such patients with a confirmed BP of at least 130/80 mm Hg, after 3 months of lifestyle intervention, pharmacologic treatment is recommended.

“This new category of elevated blood pressure recognizes that people do not go from normal blood pressure to hypertensive overnight,” Dr. McEvoy said. “It is, in most cases, a steady gradient of change, and different subgroups of patients — for example, those at a higher risk of developing cardiovascular disease — could benefit from more intensive treatment before their blood pressure reaches the traditional threshold of hypertension.”
 

New Lower Target

The major change in target pressures in these guidelines is based on new clinical trial data that confirm that lower pressures lead to lower cardiovascular event rates, resulting in the new systolic BP target of 120 mm Hg to 129 mm Hg for most patients receiving antihypertensive medications.

This systolic target represents a major change from previous European guidelines, Dr. McEvoy said, which have generally recommended that patients be treated to a target of less than 140/90 mm Hg and, only after that has been reached, then treated to a target of less than 130/80 mm Hg (a two-step approach).

“This change is driven by new trial evidence confirming that more intensive blood pressure treatment targets reduce cardiovascular outcomes across a broad spectrum of eligible patients,” Dr. McEvoy said.

There are, however, several caveats to this recommendation, including the requirement that treatment to this target be well tolerated; more lenient targets can be considered in people with symptomatic orthostatic hypotension, those 85 years and older, and those with moderate to severe frailty or a limited life expectancy. For these patients, the guidelines recommend a target “that is as low as reasonably achievable.”
 

More in Line With US Guidelines

The new European guidelines are now more in line with the American guidelines, said Eugene Yang, MD, from the University of Washington in Seattle, who is chair of the Hypertension Writing Group at the American College of Cardiology.

“These new European guidelines have thoughtfully used the latest study data to simplify recommendations for a specific lower blood pressure target. This is a step forward. There is now a greater alignment of European and US guidelines. This is good to reduce confusion and build consensus across the world,” he said.

Both sets of guidelines now recommend a BP target of less than 130/80 mm Hg for most people. 

“I think the Europeans have now embraced this more aggressive target because there are many more studies now showing that these lower blood pressure levels do lead to a reduction in cardiovascular events,” Dr. Yang explained. “When the last European guidelines came out, there was only SPRINT. Now there are several more studies showing similar results.”
 

New Lifestyle Advice

The updated recommendation of 75 minutes of vigorous-intensity aerobic exercise per week has been added as an alternative to the previous recommendation of at least 2.5 hours per week of moderate-intensity aerobic exercise. This should be complemented with low- or moderate-intensity dynamic or isometric resistance training two to three times a week. 

It is also recommended that people with hypertension, but without moderate or advanced chronic kidney disease, increase potassium intake with salt substitutes or diets rich in fruits and vegetables.
 

Renal Denervation Included for First Time 

For the first time, the guidelines include the option of renal denervation for the treatment of hypertension — at medium- to high-volume centers — for patients with resistant hypertension that is uncontrolled despite a three-drug combination.

However, renal denervation is not recommended as a first-line treatment because of the lack of evidence of a benefit in cardiovascular outcomes. It is also not recommended for patients with highly impaired renal function or secondary causes of hypertension.

Dr. Yang said he approves of the inclusion of a frailty assessment in the new guidelines and less aggressive targets for people who are in poor health and older than age 85 years, but added that, “on the whole, they have less age-specific stratification than before, which is a significant change, and a good one in my view.” 

Again, this is like the American guidelines, which have no age cutoffs and a target of less than 130/80 mm Hg for all, with the caveat that clinical judgment may be needed for individuals who are institutionalized, he added.

Dr. Yang said he was not as keen on the requirement for a cardiovascular risk assessment to guide treatment decisions for people with a systolic BP in the 130 mm Hg to 139 mm Hg range, although this is also included in the current American guidelines.

“As a clinician, I think this complicates things a bit too much and, as such, will be a barrier to treatment. In my view, blood pressure treatment recommendations need to be as simple as possible, so I think we still have some work to do there,” he said.

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

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A new consensus statement recommended genetic testing for all categories of kidney diseases whenever a genetic cause is suspected and offered guidance on who to test, which tests are the most useful, and how to talk to patients about results.

The statement, published online in the American Journal of Kidney Diseases, is the work of four dozen authors — including patients, nephrologists, experts in clinical and laboratory genetics, kidney pathology, genetic counseling, and ethics. The experts were brought together by the National Kidney Foundation (NKF) with the goal of broadening use and understanding of the tests.

About 10% or more of kidney diseases in adults and 70% of selected chronic kidney diseases (CKDs) in children have genetic causes. But nephrologists have reported a lack of education about genetic testing, and other barriers to wider use, including limited access to testing, cost, insurance coverage, and a small number of genetic counselors who are versed in kidney genetics.

Genetic testing “in the kidney field is a little less developed than in other fields,” said co–lead author Nora Franceschini, MD, MPH, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health, Chapel Hill, and a nephrologist who studies the genetic epidemiology of hypertension and kidney and cardiovascular diseases.

There are already many known variants that play a role in various kidney diseases and more are on the horizon, Dr. Franceschini told this news organization. More genetic tests will be available in the near future. “The workforce needs to be prepared,” she said.

The statement is an initial step that gets clinicians thinking about testing in a more systematic way, said Dr. Franceschini. “Genetic testing is just another test that physicians can use to complete the story when evaluating patients.

“I think clinicians are ready to implement” testing, said Dr. Franceschini. “We just need to have better guidance.”
 

Who, When, What to Test

The NKF statement is not the first to try to address gaps in use and knowledge. A European Renal Association Working Group published guidelines in 2022.

The NKF Working Group came up with 56 recommendations and separate algorithms to guide testing for adult and pediatric individuals who are considered at-risk (and currently asymptomatic) and for those who already have clinical disease.

Testing can help determine a cause if there’s an atypical clinical presentation, and it can help avoid biopsies, said the group. Tests can also guide choice of therapy.

For at-risk individuals, there are two broad situations in which testing might be considered: In family members of a patient who already has kidney disease and in potential kidney donors. But testing at-risk children younger than 18 years should only be done if there is an intervention available that could prevent, treat, or slow progression of disease, said the authors.

For patients with an established genetic diagnosis, at-risk family members should be tested with the known single-gene variant diagnostic instead of a broad panel, said the group.

Single-gene variant testing is most appropriate in situations when clinical disease is already evident or when there is known genetic disease in the family, according to the NKF panel. A large diagnostic panel that covers the many common genetic causes of kidney disease is recommended for the majority of patients.

The group recommended that apolipoprotein L1 (APOL1) testing should be included in gene panels for CKD, and it should be offered to any patient “with clinical findings suggestive of APOL1-association nephropathy, regardless of race and ethnicity.”

High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and are found in one out of seven individuals of African ancestry, which means the focus has largely been on testing those with that ancestry.

However, with many unknowns about APOL1, the NKF panel did not want to “profile” individuals and suggest that testing should not be based on skin color or race/ethnicity, said Dr. Franceschini.

In addition, only about 10% of those with the variant develop disease, so testing is not currently warranted for those who do not already have kidney disease, said the group.

They also recommended against the use of polygenic risk scores, saying that there are not enough data from diverse populations in genome-wide association studies for kidney disease or on their clinical utility.
 

More Education Needed; Many Barriers

The authors acknowledged that nephrologists generally receive little education in genetics and lack support for interpreting and discussing results.

“Nephrologists should be provided with training and best practice resources to interpret genetic testing and discuss the results with individuals and their families,” they wrote, adding that there’s a need for genomic medicine boards at academic centers that would be available to help nephrologists interpret results and plot clinical management.

The group did not, however, cite some of the other barriers to adoption of testing, including a limited number of sites offering testing, cost, and lack of insurance coverage for the diagnostics.

Medicare may cover genetic testing for kidney disease when an individual has symptoms and there is a Food and Drug Administration–approved test. Joseph Vassalotti, MD, chief medical officer for the NKF, said private insurance may cover the testing if the nephrologist deems it medically necessary, but that he usually confirms coverage before initiating testing. The often-used Renasight panel, which tests for 385 genes related to kidney diseases, costs $300-$400 out of pocket, Dr. Vassalotti told this news organization.

In a survey of 149 nephrologists conducted in 2021, both users (46%) and nonusers of the tests (69%) said that high cost was the most significant perceived barrier to implementing widespread testing. A third of users and almost two thirds of nonusers said that poor availability or lack of ease of testing was the second most significant barrier.

Clinics that test for kidney genes “are largely confined to large academic centers and some specialty clinics,” said Dominic Raj, MD, the Bert B. Brooks chair, and Divya Shankaranarayanan, MD, director of the Kidney Precision Medicine Clinic, both at George Washington University School of Medicine & Health Sciences, Washington, DC, in an email.

Testing is also limited by cultural barriers, lack of genetic literacy, and patients’ concerns that a positive result could lead to a loss of health insurance coverage, said Dr. Raj and Dr. Shankaranarayanan.
 

Paper Will Help Expand Use

A lack of consensus has also held back expansion. The new statement “may lead to increased and possibly judicious utilization of genetic testing in nephrology practices,” said Dr. Raj and Dr. Shankaranarayanan. “Most importantly, the panel has given specific guidance as to what type of genetic test platform is likely to yield the best and most cost-effective yield.”

The most effective use is “in monogenic kidney diseases and to a lesser extent in oligogenic kidney disease,” said Dr. Raj and Dr. Shankaranarayanan, adding that testing is of less-certain utility in polygenic kidney diseases, “where complex genetic and epigenetic factors determine the phenotype.”

Genetic testing might be especially useful “in atypical clinical presentations” and can help clinicians avoid unnecessary expensive and extensive investigations when multiple organ systems are involved, they said.

“Most importantly, [testing] might prevent unnecessary and potentially harmful treatment and enable targeted specific treatment, when available,” said Dr. Raj and Dr. Shankaranarayanan.

Dr. Franceschini and Dr. Shankaranarayanan reported no relevant financial relationships. Dr. Raj disclosed that he received consulting fees and honoraria from Novo Nordisk and is a national leader for the company’s Zeus trial, studying whether ziltivekimab reduces the risk for cardiovascular events in cardiovascular disease, CKD, and inflammation. He also participated in a study of Natera’s Renasight, a 385-gene panel for kidney disease.

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

A new consensus statement recommended genetic testing for all categories of kidney diseases whenever a genetic cause is suspected and offered guidance on who to test, which tests are the most useful, and how to talk to patients about results.

The statement, published online in the American Journal of Kidney Diseases, is the work of four dozen authors — including patients, nephrologists, experts in clinical and laboratory genetics, kidney pathology, genetic counseling, and ethics. The experts were brought together by the National Kidney Foundation (NKF) with the goal of broadening use and understanding of the tests.

About 10% or more of kidney diseases in adults and 70% of selected chronic kidney diseases (CKDs) in children have genetic causes. But nephrologists have reported a lack of education about genetic testing, and other barriers to wider use, including limited access to testing, cost, insurance coverage, and a small number of genetic counselors who are versed in kidney genetics.

Genetic testing “in the kidney field is a little less developed than in other fields,” said co–lead author Nora Franceschini, MD, MPH, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health, Chapel Hill, and a nephrologist who studies the genetic epidemiology of hypertension and kidney and cardiovascular diseases.

There are already many known variants that play a role in various kidney diseases and more are on the horizon, Dr. Franceschini told this news organization. More genetic tests will be available in the near future. “The workforce needs to be prepared,” she said.

The statement is an initial step that gets clinicians thinking about testing in a more systematic way, said Dr. Franceschini. “Genetic testing is just another test that physicians can use to complete the story when evaluating patients.

“I think clinicians are ready to implement” testing, said Dr. Franceschini. “We just need to have better guidance.”
 

Who, When, What to Test

The NKF statement is not the first to try to address gaps in use and knowledge. A European Renal Association Working Group published guidelines in 2022.

The NKF Working Group came up with 56 recommendations and separate algorithms to guide testing for adult and pediatric individuals who are considered at-risk (and currently asymptomatic) and for those who already have clinical disease.

Testing can help determine a cause if there’s an atypical clinical presentation, and it can help avoid biopsies, said the group. Tests can also guide choice of therapy.

For at-risk individuals, there are two broad situations in which testing might be considered: In family members of a patient who already has kidney disease and in potential kidney donors. But testing at-risk children younger than 18 years should only be done if there is an intervention available that could prevent, treat, or slow progression of disease, said the authors.

For patients with an established genetic diagnosis, at-risk family members should be tested with the known single-gene variant diagnostic instead of a broad panel, said the group.

Single-gene variant testing is most appropriate in situations when clinical disease is already evident or when there is known genetic disease in the family, according to the NKF panel. A large diagnostic panel that covers the many common genetic causes of kidney disease is recommended for the majority of patients.

The group recommended that apolipoprotein L1 (APOL1) testing should be included in gene panels for CKD, and it should be offered to any patient “with clinical findings suggestive of APOL1-association nephropathy, regardless of race and ethnicity.”

High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and are found in one out of seven individuals of African ancestry, which means the focus has largely been on testing those with that ancestry.

However, with many unknowns about APOL1, the NKF panel did not want to “profile” individuals and suggest that testing should not be based on skin color or race/ethnicity, said Dr. Franceschini.

In addition, only about 10% of those with the variant develop disease, so testing is not currently warranted for those who do not already have kidney disease, said the group.

They also recommended against the use of polygenic risk scores, saying that there are not enough data from diverse populations in genome-wide association studies for kidney disease or on their clinical utility.
 

More Education Needed; Many Barriers

The authors acknowledged that nephrologists generally receive little education in genetics and lack support for interpreting and discussing results.

“Nephrologists should be provided with training and best practice resources to interpret genetic testing and discuss the results with individuals and their families,” they wrote, adding that there’s a need for genomic medicine boards at academic centers that would be available to help nephrologists interpret results and plot clinical management.

The group did not, however, cite some of the other barriers to adoption of testing, including a limited number of sites offering testing, cost, and lack of insurance coverage for the diagnostics.

Medicare may cover genetic testing for kidney disease when an individual has symptoms and there is a Food and Drug Administration–approved test. Joseph Vassalotti, MD, chief medical officer for the NKF, said private insurance may cover the testing if the nephrologist deems it medically necessary, but that he usually confirms coverage before initiating testing. The often-used Renasight panel, which tests for 385 genes related to kidney diseases, costs $300-$400 out of pocket, Dr. Vassalotti told this news organization.

In a survey of 149 nephrologists conducted in 2021, both users (46%) and nonusers of the tests (69%) said that high cost was the most significant perceived barrier to implementing widespread testing. A third of users and almost two thirds of nonusers said that poor availability or lack of ease of testing was the second most significant barrier.

Clinics that test for kidney genes “are largely confined to large academic centers and some specialty clinics,” said Dominic Raj, MD, the Bert B. Brooks chair, and Divya Shankaranarayanan, MD, director of the Kidney Precision Medicine Clinic, both at George Washington University School of Medicine & Health Sciences, Washington, DC, in an email.

Testing is also limited by cultural barriers, lack of genetic literacy, and patients’ concerns that a positive result could lead to a loss of health insurance coverage, said Dr. Raj and Dr. Shankaranarayanan.
 

Paper Will Help Expand Use

A lack of consensus has also held back expansion. The new statement “may lead to increased and possibly judicious utilization of genetic testing in nephrology practices,” said Dr. Raj and Dr. Shankaranarayanan. “Most importantly, the panel has given specific guidance as to what type of genetic test platform is likely to yield the best and most cost-effective yield.”

The most effective use is “in monogenic kidney diseases and to a lesser extent in oligogenic kidney disease,” said Dr. Raj and Dr. Shankaranarayanan, adding that testing is of less-certain utility in polygenic kidney diseases, “where complex genetic and epigenetic factors determine the phenotype.”

Genetic testing might be especially useful “in atypical clinical presentations” and can help clinicians avoid unnecessary expensive and extensive investigations when multiple organ systems are involved, they said.

“Most importantly, [testing] might prevent unnecessary and potentially harmful treatment and enable targeted specific treatment, when available,” said Dr. Raj and Dr. Shankaranarayanan.

Dr. Franceschini and Dr. Shankaranarayanan reported no relevant financial relationships. Dr. Raj disclosed that he received consulting fees and honoraria from Novo Nordisk and is a national leader for the company’s Zeus trial, studying whether ziltivekimab reduces the risk for cardiovascular events in cardiovascular disease, CKD, and inflammation. He also participated in a study of Natera’s Renasight, a 385-gene panel for kidney disease.

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

A new consensus statement recommended genetic testing for all categories of kidney diseases whenever a genetic cause is suspected and offered guidance on who to test, which tests are the most useful, and how to talk to patients about results.

The statement, published online in the American Journal of Kidney Diseases, is the work of four dozen authors — including patients, nephrologists, experts in clinical and laboratory genetics, kidney pathology, genetic counseling, and ethics. The experts were brought together by the National Kidney Foundation (NKF) with the goal of broadening use and understanding of the tests.

About 10% or more of kidney diseases in adults and 70% of selected chronic kidney diseases (CKDs) in children have genetic causes. But nephrologists have reported a lack of education about genetic testing, and other barriers to wider use, including limited access to testing, cost, insurance coverage, and a small number of genetic counselors who are versed in kidney genetics.

Genetic testing “in the kidney field is a little less developed than in other fields,” said co–lead author Nora Franceschini, MD, MPH, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health, Chapel Hill, and a nephrologist who studies the genetic epidemiology of hypertension and kidney and cardiovascular diseases.

There are already many known variants that play a role in various kidney diseases and more are on the horizon, Dr. Franceschini told this news organization. More genetic tests will be available in the near future. “The workforce needs to be prepared,” she said.

The statement is an initial step that gets clinicians thinking about testing in a more systematic way, said Dr. Franceschini. “Genetic testing is just another test that physicians can use to complete the story when evaluating patients.

“I think clinicians are ready to implement” testing, said Dr. Franceschini. “We just need to have better guidance.”
 

Who, When, What to Test

The NKF statement is not the first to try to address gaps in use and knowledge. A European Renal Association Working Group published guidelines in 2022.

The NKF Working Group came up with 56 recommendations and separate algorithms to guide testing for adult and pediatric individuals who are considered at-risk (and currently asymptomatic) and for those who already have clinical disease.

Testing can help determine a cause if there’s an atypical clinical presentation, and it can help avoid biopsies, said the group. Tests can also guide choice of therapy.

For at-risk individuals, there are two broad situations in which testing might be considered: In family members of a patient who already has kidney disease and in potential kidney donors. But testing at-risk children younger than 18 years should only be done if there is an intervention available that could prevent, treat, or slow progression of disease, said the authors.

For patients with an established genetic diagnosis, at-risk family members should be tested with the known single-gene variant diagnostic instead of a broad panel, said the group.

Single-gene variant testing is most appropriate in situations when clinical disease is already evident or when there is known genetic disease in the family, according to the NKF panel. A large diagnostic panel that covers the many common genetic causes of kidney disease is recommended for the majority of patients.

The group recommended that apolipoprotein L1 (APOL1) testing should be included in gene panels for CKD, and it should be offered to any patient “with clinical findings suggestive of APOL1-association nephropathy, regardless of race and ethnicity.”

High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and are found in one out of seven individuals of African ancestry, which means the focus has largely been on testing those with that ancestry.

However, with many unknowns about APOL1, the NKF panel did not want to “profile” individuals and suggest that testing should not be based on skin color or race/ethnicity, said Dr. Franceschini.

In addition, only about 10% of those with the variant develop disease, so testing is not currently warranted for those who do not already have kidney disease, said the group.

They also recommended against the use of polygenic risk scores, saying that there are not enough data from diverse populations in genome-wide association studies for kidney disease or on their clinical utility.
 

More Education Needed; Many Barriers

The authors acknowledged that nephrologists generally receive little education in genetics and lack support for interpreting and discussing results.

“Nephrologists should be provided with training and best practice resources to interpret genetic testing and discuss the results with individuals and their families,” they wrote, adding that there’s a need for genomic medicine boards at academic centers that would be available to help nephrologists interpret results and plot clinical management.

The group did not, however, cite some of the other barriers to adoption of testing, including a limited number of sites offering testing, cost, and lack of insurance coverage for the diagnostics.

Medicare may cover genetic testing for kidney disease when an individual has symptoms and there is a Food and Drug Administration–approved test. Joseph Vassalotti, MD, chief medical officer for the NKF, said private insurance may cover the testing if the nephrologist deems it medically necessary, but that he usually confirms coverage before initiating testing. The often-used Renasight panel, which tests for 385 genes related to kidney diseases, costs $300-$400 out of pocket, Dr. Vassalotti told this news organization.

In a survey of 149 nephrologists conducted in 2021, both users (46%) and nonusers of the tests (69%) said that high cost was the most significant perceived barrier to implementing widespread testing. A third of users and almost two thirds of nonusers said that poor availability or lack of ease of testing was the second most significant barrier.

Clinics that test for kidney genes “are largely confined to large academic centers and some specialty clinics,” said Dominic Raj, MD, the Bert B. Brooks chair, and Divya Shankaranarayanan, MD, director of the Kidney Precision Medicine Clinic, both at George Washington University School of Medicine & Health Sciences, Washington, DC, in an email.

Testing is also limited by cultural barriers, lack of genetic literacy, and patients’ concerns that a positive result could lead to a loss of health insurance coverage, said Dr. Raj and Dr. Shankaranarayanan.
 

Paper Will Help Expand Use

A lack of consensus has also held back expansion. The new statement “may lead to increased and possibly judicious utilization of genetic testing in nephrology practices,” said Dr. Raj and Dr. Shankaranarayanan. “Most importantly, the panel has given specific guidance as to what type of genetic test platform is likely to yield the best and most cost-effective yield.”

The most effective use is “in monogenic kidney diseases and to a lesser extent in oligogenic kidney disease,” said Dr. Raj and Dr. Shankaranarayanan, adding that testing is of less-certain utility in polygenic kidney diseases, “where complex genetic and epigenetic factors determine the phenotype.”

Genetic testing might be especially useful “in atypical clinical presentations” and can help clinicians avoid unnecessary expensive and extensive investigations when multiple organ systems are involved, they said.

“Most importantly, [testing] might prevent unnecessary and potentially harmful treatment and enable targeted specific treatment, when available,” said Dr. Raj and Dr. Shankaranarayanan.

Dr. Franceschini and Dr. Shankaranarayanan reported no relevant financial relationships. Dr. Raj disclosed that he received consulting fees and honoraria from Novo Nordisk and is a national leader for the company’s Zeus trial, studying whether ziltivekimab reduces the risk for cardiovascular events in cardiovascular disease, CKD, and inflammation. He also participated in a study of Natera’s Renasight, a 385-gene panel for kidney disease.

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

TOPLINE:

A study found significant associations between melasma and several comorbidities, including hypertension and hormonal contraception use, which were the most common.

METHODOLOGY:

• Melasma predominantly affects young women of color and often worsens in hyperestrogen states; understanding the association with comorbidities can improve surveillance and treatment strategies.
• Researchers evaluated 41,283 patients with melasma (mean age, 48.8 years; 93% women) from the TriNetX database and an equal number of matched control individuals.
• The main outcome was comorbidities including allergic rhinitis, atopic dermatitis, anticonvulsants, diabetes, hormonal contraceptives, hypothyroidism, hypertension, lupus, rosacea, skin cancer, and malignancy.

TAKEAWAY:

• Among those with melasma, 25% had hypertension and 24% used hormonal contraception, the two most commonly associated risk factors identified.
• Rosacea (odds ratio [OR], 5.1), atopic dermatitis (OR, 3.3), lupus (OR, 2.5), history of skin cancer (OR, 2.5), and history of internal malignancy (OR, 2.1) were associated with the highest risk of developing melasma (P < .01 for all).
• Asian (OR, 2.0; P < .01) and “other/unknown” races (OR, 1.7; P < .01) and Hispanic ethnicity (OR, 1.3; P < .01) were also significantly associated with melasma, while the odds were slightly lower among White, Black/African American, and “not Hispanic” groups (ORs, 0.8; P < .01 for all groups).

IN PRACTICE:

“Understanding the potential associations between these risk factors and melasma will better improve the management and monitoring of the most susceptible patients,” the authors wrote.

SOURCE:

The study, led by Ajay N. Sharma, MD, MBA, of the Department of Dermatology at the University of California, Irvine, was published online in Journal of Drugs in Dermatology.

LIMITATIONS:

The study limitations included the retrospective design, potential misclassification of diagnoses, and the inability to establish causality.

DISCLOSURES:

The study did not disclose any funding sources. The authors declared no conflicts of interest.

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

TOPLINE:

A study found significant associations between melasma and several comorbidities, including hypertension and hormonal contraception use, which were the most common.

METHODOLOGY:

• Melasma predominantly affects young women of color and often worsens in hyperestrogen states; understanding the association with comorbidities can improve surveillance and treatment strategies.
• Researchers evaluated 41,283 patients with melasma (mean age, 48.8 years; 93% women) from the TriNetX database and an equal number of matched control individuals.
• The main outcome was comorbidities including allergic rhinitis, atopic dermatitis, anticonvulsants, diabetes, hormonal contraceptives, hypothyroidism, hypertension, lupus, rosacea, skin cancer, and malignancy.

TAKEAWAY:

• Among those with melasma, 25% had hypertension and 24% used hormonal contraception, the two most commonly associated risk factors identified.
• Rosacea (odds ratio [OR], 5.1), atopic dermatitis (OR, 3.3), lupus (OR, 2.5), history of skin cancer (OR, 2.5), and history of internal malignancy (OR, 2.1) were associated with the highest risk of developing melasma (P < .01 for all).
• Asian (OR, 2.0; P < .01) and “other/unknown” races (OR, 1.7; P < .01) and Hispanic ethnicity (OR, 1.3; P < .01) were also significantly associated with melasma, while the odds were slightly lower among White, Black/African American, and “not Hispanic” groups (ORs, 0.8; P < .01 for all groups).

IN PRACTICE:

“Understanding the potential associations between these risk factors and melasma will better improve the management and monitoring of the most susceptible patients,” the authors wrote.

SOURCE:

The study, led by Ajay N. Sharma, MD, MBA, of the Department of Dermatology at the University of California, Irvine, was published online in Journal of Drugs in Dermatology.

LIMITATIONS:

The study limitations included the retrospective design, potential misclassification of diagnoses, and the inability to establish causality.

DISCLOSURES:

The study did not disclose any funding sources. The authors declared no conflicts of interest.

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

TOPLINE:

A study found significant associations between melasma and several comorbidities, including hypertension and hormonal contraception use, which were the most common.

METHODOLOGY:

• Melasma predominantly affects young women of color and often worsens in hyperestrogen states; understanding the association with comorbidities can improve surveillance and treatment strategies.
• Researchers evaluated 41,283 patients with melasma (mean age, 48.8 years; 93% women) from the TriNetX database and an equal number of matched control individuals.
• The main outcome was comorbidities including allergic rhinitis, atopic dermatitis, anticonvulsants, diabetes, hormonal contraceptives, hypothyroidism, hypertension, lupus, rosacea, skin cancer, and malignancy.

TAKEAWAY:

• Among those with melasma, 25% had hypertension and 24% used hormonal contraception, the two most commonly associated risk factors identified.
• Rosacea (odds ratio [OR], 5.1), atopic dermatitis (OR, 3.3), lupus (OR, 2.5), history of skin cancer (OR, 2.5), and history of internal malignancy (OR, 2.1) were associated with the highest risk of developing melasma (P < .01 for all).
• Asian (OR, 2.0; P < .01) and “other/unknown” races (OR, 1.7; P < .01) and Hispanic ethnicity (OR, 1.3; P < .01) were also significantly associated with melasma, while the odds were slightly lower among White, Black/African American, and “not Hispanic” groups (ORs, 0.8; P < .01 for all groups).

IN PRACTICE:

“Understanding the potential associations between these risk factors and melasma will better improve the management and monitoring of the most susceptible patients,” the authors wrote.

SOURCE:

The study, led by Ajay N. Sharma, MD, MBA, of the Department of Dermatology at the University of California, Irvine, was published online in Journal of Drugs in Dermatology.

LIMITATIONS:

The study limitations included the retrospective design, potential misclassification of diagnoses, and the inability to establish causality.

DISCLOSURES:

The study did not disclose any funding sources. The authors declared no conflicts of interest.

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

Progression of chronic kidney disease (CKD) and cardiovascular disease risk in hypertensive adults was significantly slower among those who consumed more fruits and vegetables or oral sodium bicarbonate, compared with controls who received usual care.

A primary focus on pharmacologic strategies has failed to reduced hypertension-related CKD and cardiovascular disease mortality, Nimrit Goraya, MD, of Texas A&M Health Sciences Center College of Medicine, Temple, and colleagues wrote. High-acid diets (those with greater amounts of animal-sourced foods) have been associated with increased incidence and progression of CKD and with increased risk of cardiovascular disease.

Diets high in fruits and vegetables are associated with reduced CKD and cardiovascular disease but are not routinely used as part of hypertension treatment. The researchers hypothesized that dietary acid reduction could slow kidney disease progression and reduce cardiovascular disease risk.

In a study published in The American Journal of Medicine, the researchers randomized 153 adults aged 18-70 years with hypertension and CKD to fruits and vegetables, oral sodium bicarbonate (NaHCO₃), or usual care; 51 to each group. The fruit and vegetable group received 2-4 cups daily of base-producing food items including apples, apricots, oranges, peaches, pears, raisins, strawberries, carrots, cauliflower, eggplant, lettuce, potatoes, spinach, tomatoes, and zucchini. Participants were not instructed how to incorporate these foods into their diets. The sodium bicarbonate group received an average of four to five NaHCO₃ tablets daily (650 mg), divided into two doses.

The mean age of the participants was 48.8 years, 51% were female, and 47% were African American. The primary outcome was CKD progression and cardiovascular disease risk over 5 years. All participants met criteria at baseline for macroalbuminuria (a urine albumin to creatinine ratio of at least 200 mg/g) and were considered at increased risk for CKD progression.

Over the 5-year follow-up, CKD progression was significantly slower in the groups receiving fruits and vegetables and oral sodium bicarbonate, compared with usual care, based on trajectories showing a lower decline of estimated glomerular filtration rates (mean declines of 1.08 and 1.17 for fruits/vegetables and NaHCO₃, respectively, vs 19.4 for usual care, P < .001 for both).

However, systolic blood pressure and subsequent cardiovascular disease risk indicators were lower only in the fruit and vegetable group, compared with both the NaHCO₃ or usual-care groups over the long term. “Specifically, with fruits and vegetables, systolic blood pressure, plasma LDL and Lp(a) cholesterol, and body mass index decreased from baseline, consistent with better cardiovascular disease protection,” the researchers wrote. The protection against cardiovascular disease in the fruits and vegetables group occurred with lower doses of antihypertensive and statin medications and was not affected by baseline differences in medication doses.

The findings were limited by several factors, including the lack of data on compliance with the NaHCO₃ supplements, although urine net acid excretion in this group suggested increased alkali intake similar to that provided by fruits and vegetables, the researchers noted. Other limitations included the focus only on individuals with very high albuminuria.

More basic science studies are needed to explore how the potential vascular injury suggested by albuminuria affects CKD progression and cardiovascular disease, and clinical studies are needed to assess the impact of dietary acid reduction on patients with lower levels of albuminuria that the current study, the researchers said.

However, the results suggest that consuming fruits and vegetables, rather than NaHCO₃, is the preferred strategy for dietary acid reduction for patients with primary hypertension and CKD, they concluded. The findings also support routine measurement of urine albumin-to-creatinine ratios in hypertensive patients to identify CKD and assess risk for progression and subsequent cardiovascular disease.

The study was supported by the Larry and Jane Woirhaye Memorial Endowment in Renal Research at the Texas Tech University Health Sciences Center, the University Medical Center (both in Lubbock, Texas), the Endowment, Academic Operations Division of Baylor Scott & White Health, and the Episcopal Health Foundation. The researchers had no financial conflicts to disclose.

Progression of chronic kidney disease (CKD) and cardiovascular disease risk in hypertensive adults was significantly slower among those who consumed more fruits and vegetables or oral sodium bicarbonate, compared with controls who received usual care.

A primary focus on pharmacologic strategies has failed to reduced hypertension-related CKD and cardiovascular disease mortality, Nimrit Goraya, MD, of Texas A&M Health Sciences Center College of Medicine, Temple, and colleagues wrote. High-acid diets (those with greater amounts of animal-sourced foods) have been associated with increased incidence and progression of CKD and with increased risk of cardiovascular disease.

Diets high in fruits and vegetables are associated with reduced CKD and cardiovascular disease but are not routinely used as part of hypertension treatment. The researchers hypothesized that dietary acid reduction could slow kidney disease progression and reduce cardiovascular disease risk.

In a study published in The American Journal of Medicine, the researchers randomized 153 adults aged 18-70 years with hypertension and CKD to fruits and vegetables, oral sodium bicarbonate (NaHCO₃), or usual care; 51 to each group. The fruit and vegetable group received 2-4 cups daily of base-producing food items including apples, apricots, oranges, peaches, pears, raisins, strawberries, carrots, cauliflower, eggplant, lettuce, potatoes, spinach, tomatoes, and zucchini. Participants were not instructed how to incorporate these foods into their diets. The sodium bicarbonate group received an average of four to five NaHCO₃ tablets daily (650 mg), divided into two doses.

The mean age of the participants was 48.8 years, 51% were female, and 47% were African American. The primary outcome was CKD progression and cardiovascular disease risk over 5 years. All participants met criteria at baseline for macroalbuminuria (a urine albumin to creatinine ratio of at least 200 mg/g) and were considered at increased risk for CKD progression.

Over the 5-year follow-up, CKD progression was significantly slower in the groups receiving fruits and vegetables and oral sodium bicarbonate, compared with usual care, based on trajectories showing a lower decline of estimated glomerular filtration rates (mean declines of 1.08 and 1.17 for fruits/vegetables and NaHCO₃, respectively, vs 19.4 for usual care, P < .001 for both).

However, systolic blood pressure and subsequent cardiovascular disease risk indicators were lower only in the fruit and vegetable group, compared with both the NaHCO₃ or usual-care groups over the long term. “Specifically, with fruits and vegetables, systolic blood pressure, plasma LDL and Lp(a) cholesterol, and body mass index decreased from baseline, consistent with better cardiovascular disease protection,” the researchers wrote. The protection against cardiovascular disease in the fruits and vegetables group occurred with lower doses of antihypertensive and statin medications and was not affected by baseline differences in medication doses.

The findings were limited by several factors, including the lack of data on compliance with the NaHCO₃ supplements, although urine net acid excretion in this group suggested increased alkali intake similar to that provided by fruits and vegetables, the researchers noted. Other limitations included the focus only on individuals with very high albuminuria.

More basic science studies are needed to explore how the potential vascular injury suggested by albuminuria affects CKD progression and cardiovascular disease, and clinical studies are needed to assess the impact of dietary acid reduction on patients with lower levels of albuminuria that the current study, the researchers said.

However, the results suggest that consuming fruits and vegetables, rather than NaHCO₃, is the preferred strategy for dietary acid reduction for patients with primary hypertension and CKD, they concluded. The findings also support routine measurement of urine albumin-to-creatinine ratios in hypertensive patients to identify CKD and assess risk for progression and subsequent cardiovascular disease.

The study was supported by the Larry and Jane Woirhaye Memorial Endowment in Renal Research at the Texas Tech University Health Sciences Center, the University Medical Center (both in Lubbock, Texas), the Endowment, Academic Operations Division of Baylor Scott & White Health, and the Episcopal Health Foundation. The researchers had no financial conflicts to disclose.

Progression of chronic kidney disease (CKD) and cardiovascular disease risk in hypertensive adults was significantly slower among those who consumed more fruits and vegetables or oral sodium bicarbonate, compared with controls who received usual care.

A primary focus on pharmacologic strategies has failed to reduced hypertension-related CKD and cardiovascular disease mortality, Nimrit Goraya, MD, of Texas A&M Health Sciences Center College of Medicine, Temple, and colleagues wrote. High-acid diets (those with greater amounts of animal-sourced foods) have been associated with increased incidence and progression of CKD and with increased risk of cardiovascular disease.

Diets high in fruits and vegetables are associated with reduced CKD and cardiovascular disease but are not routinely used as part of hypertension treatment. The researchers hypothesized that dietary acid reduction could slow kidney disease progression and reduce cardiovascular disease risk.

In a study published in The American Journal of Medicine, the researchers randomized 153 adults aged 18-70 years with hypertension and CKD to fruits and vegetables, oral sodium bicarbonate (NaHCO₃), or usual care; 51 to each group. The fruit and vegetable group received 2-4 cups daily of base-producing food items including apples, apricots, oranges, peaches, pears, raisins, strawberries, carrots, cauliflower, eggplant, lettuce, potatoes, spinach, tomatoes, and zucchini. Participants were not instructed how to incorporate these foods into their diets. The sodium bicarbonate group received an average of four to five NaHCO₃ tablets daily (650 mg), divided into two doses.

The mean age of the participants was 48.8 years, 51% were female, and 47% were African American. The primary outcome was CKD progression and cardiovascular disease risk over 5 years. All participants met criteria at baseline for macroalbuminuria (a urine albumin to creatinine ratio of at least 200 mg/g) and were considered at increased risk for CKD progression.

Over the 5-year follow-up, CKD progression was significantly slower in the groups receiving fruits and vegetables and oral sodium bicarbonate, compared with usual care, based on trajectories showing a lower decline of estimated glomerular filtration rates (mean declines of 1.08 and 1.17 for fruits/vegetables and NaHCO₃, respectively, vs 19.4 for usual care, P < .001 for both).

However, systolic blood pressure and subsequent cardiovascular disease risk indicators were lower only in the fruit and vegetable group, compared with both the NaHCO₃ or usual-care groups over the long term. “Specifically, with fruits and vegetables, systolic blood pressure, plasma LDL and Lp(a) cholesterol, and body mass index decreased from baseline, consistent with better cardiovascular disease protection,” the researchers wrote. The protection against cardiovascular disease in the fruits and vegetables group occurred with lower doses of antihypertensive and statin medications and was not affected by baseline differences in medication doses.

The findings were limited by several factors, including the lack of data on compliance with the NaHCO₃ supplements, although urine net acid excretion in this group suggested increased alkali intake similar to that provided by fruits and vegetables, the researchers noted. Other limitations included the focus only on individuals with very high albuminuria.

More basic science studies are needed to explore how the potential vascular injury suggested by albuminuria affects CKD progression and cardiovascular disease, and clinical studies are needed to assess the impact of dietary acid reduction on patients with lower levels of albuminuria that the current study, the researchers said.

However, the results suggest that consuming fruits and vegetables, rather than NaHCO₃, is the preferred strategy for dietary acid reduction for patients with primary hypertension and CKD, they concluded. The findings also support routine measurement of urine albumin-to-creatinine ratios in hypertensive patients to identify CKD and assess risk for progression and subsequent cardiovascular disease.

The study was supported by the Larry and Jane Woirhaye Memorial Endowment in Renal Research at the Texas Tech University Health Sciences Center, the University Medical Center (both in Lubbock, Texas), the Endowment, Academic Operations Division of Baylor Scott & White Health, and the Episcopal Health Foundation. The researchers had no financial conflicts to disclose.