Cardiology News

When it comes to dieting and heart health in patients who are also exercising, less is more, suggests a new study.

The authors of the paper, published in Circulation, found a link between greater vascular benefits and exercise with modest – rather than intense – calorie restriction (CR) in elderly individuals with obesity.

“The finding that higher-intensity calorie restriction may not be necessary or advised has important implications for weight loss recommendations,” noted Tina E. Brinkley, Ph.D., lead author of the study and associate professor of gerontology and geriatric medicine at the Sticht Center for Healthy Aging and Alzheimer’s Prevention at Wake Forest University in Winston-Salem, N.C.

It’s “not entirely clear” why greater calorie restriction did not translate to greater vascular benefit, but it “could be related in part to potentially adverse effects of severe CR on vascular function,” she noted. “These findings have important implications for reducing cardiovascular risk with nonpharmacological interventions in high-risk populations.”

Methods and findings

The study included 160 men and women aged 65-79 years, with a body mass index (BMI) of 30 to 45 kg/m². The subjects were randomized to one of three groups for 20 weeks of aerobic exercise only, aerobic exercise plus moderate CR, or aerobic exercise plus more intensive CR. Their exercise regimen involved 30 minutes of supervised treadmill walking for 4 days per week at 65%-70% of heart rate reserve.

Subjects in the moderate CR group decreased caloric intake by 250 kcals a day, while the intense calorie reduction group cut 600 kcals per day. Their meals contained less than 30% of calories from fat and at least 0.8 g of protein per kg of ideal body weight. They were also provided with supplemental calcium (1,200 mg/day) and vitamin D (800 IU/day).

Cardiovascular magnetic resonance imaging was used to assess various aspects of aortic structure and function, including aortic arch pulse wave velocity, aortic distensibility and dimensions, and periaortic fat.

Weight loss was greater among subjects with CR plus exercise, compared with that of patients in the exercise-only group. The degree of weight loss was not significantly different between those with moderate versus intense CR ( 8.02 kg vs. 8.98 kg).

Among the exercise-only group, researchers observed no changes in aortic stiffness. However, adding moderate CR significantly improved this measure, while intense CR did not.

Specifically, subjects in the moderate-CR group had a “robust” 21% increase in distensibility in the descending aorta (DA), and an 8% decrease in aortic arch pulse wave velocity, whereas there were no significant vascular changes in the intense-CR group.

Bests results seen in exercise plus modest CR group

“Collectively, these data suggest that combining exercise with modest CR (as opposed to more intensive CR or no CR) provides the greatest benefit for proximal aortic stiffness, while also optimizing weight loss and improvements in body composition and body fat distribution,” noted the authors in their paper.

“Our data support the growing number of studies indicating that intentional weight loss can be safe for older adults with obesity and extend our previous findings, suggesting that obesity may blunt the beneficial effects of exercise for not only cardiorespiratory fitness, but likely vascular health as well.”

William E. Kraus, MD, professor in the Department of Medicine, Division of Cardiology at Duke University Medical Center, in Durham, NC, described the study as important and interesting for several reasons.

“First, it demonstrates one can change aortic vascular function with a combined diet and exercise program, even in older, obese Americans. This implies it is never too late to make meaningful lifestyle changes that will benefit cardiovascular health,” he said. “Second, it is among an increasing number of studies demonstrating that more is not always better than less in exercise and diet lifestyle changes - and in fact the converse is true.” 

“This gives hope that more people can benefit from modest lifestyle changes - in this case following guidelines for physical activity and only a modest reduction of 250 kilocalories per day resulted in benefit,” Dr. Kraus added.

The authors of the paper and Dr. Kraus disclosed no conflicts of interest.

When it comes to dieting and heart health in patients who are also exercising, less is more, suggests a new study.

The authors of the paper, published in Circulation, found a link between greater vascular benefits and exercise with modest – rather than intense – calorie restriction (CR) in elderly individuals with obesity.

“The finding that higher-intensity calorie restriction may not be necessary or advised has important implications for weight loss recommendations,” noted Tina E. Brinkley, Ph.D., lead author of the study and associate professor of gerontology and geriatric medicine at the Sticht Center for Healthy Aging and Alzheimer’s Prevention at Wake Forest University in Winston-Salem, N.C.

It’s “not entirely clear” why greater calorie restriction did not translate to greater vascular benefit, but it “could be related in part to potentially adverse effects of severe CR on vascular function,” she noted. “These findings have important implications for reducing cardiovascular risk with nonpharmacological interventions in high-risk populations.”

Methods and findings

The study included 160 men and women aged 65-79 years, with a body mass index (BMI) of 30 to 45 kg/m². The subjects were randomized to one of three groups for 20 weeks of aerobic exercise only, aerobic exercise plus moderate CR, or aerobic exercise plus more intensive CR. Their exercise regimen involved 30 minutes of supervised treadmill walking for 4 days per week at 65%-70% of heart rate reserve.

Subjects in the moderate CR group decreased caloric intake by 250 kcals a day, while the intense calorie reduction group cut 600 kcals per day. Their meals contained less than 30% of calories from fat and at least 0.8 g of protein per kg of ideal body weight. They were also provided with supplemental calcium (1,200 mg/day) and vitamin D (800 IU/day).

Cardiovascular magnetic resonance imaging was used to assess various aspects of aortic structure and function, including aortic arch pulse wave velocity, aortic distensibility and dimensions, and periaortic fat.

Weight loss was greater among subjects with CR plus exercise, compared with that of patients in the exercise-only group. The degree of weight loss was not significantly different between those with moderate versus intense CR ( 8.02 kg vs. 8.98 kg).

Among the exercise-only group, researchers observed no changes in aortic stiffness. However, adding moderate CR significantly improved this measure, while intense CR did not.

Specifically, subjects in the moderate-CR group had a “robust” 21% increase in distensibility in the descending aorta (DA), and an 8% decrease in aortic arch pulse wave velocity, whereas there were no significant vascular changes in the intense-CR group.

Bests results seen in exercise plus modest CR group

“Collectively, these data suggest that combining exercise with modest CR (as opposed to more intensive CR or no CR) provides the greatest benefit for proximal aortic stiffness, while also optimizing weight loss and improvements in body composition and body fat distribution,” noted the authors in their paper.

“Our data support the growing number of studies indicating that intentional weight loss can be safe for older adults with obesity and extend our previous findings, suggesting that obesity may blunt the beneficial effects of exercise for not only cardiorespiratory fitness, but likely vascular health as well.”

William E. Kraus, MD, professor in the Department of Medicine, Division of Cardiology at Duke University Medical Center, in Durham, NC, described the study as important and interesting for several reasons.

“First, it demonstrates one can change aortic vascular function with a combined diet and exercise program, even in older, obese Americans. This implies it is never too late to make meaningful lifestyle changes that will benefit cardiovascular health,” he said. “Second, it is among an increasing number of studies demonstrating that more is not always better than less in exercise and diet lifestyle changes - and in fact the converse is true.” 

“This gives hope that more people can benefit from modest lifestyle changes - in this case following guidelines for physical activity and only a modest reduction of 250 kilocalories per day resulted in benefit,” Dr. Kraus added.

The authors of the paper and Dr. Kraus disclosed no conflicts of interest.

When it comes to dieting and heart health in patients who are also exercising, less is more, suggests a new study.

The authors of the paper, published in Circulation, found a link between greater vascular benefits and exercise with modest – rather than intense – calorie restriction (CR) in elderly individuals with obesity.

“The finding that higher-intensity calorie restriction may not be necessary or advised has important implications for weight loss recommendations,” noted Tina E. Brinkley, Ph.D., lead author of the study and associate professor of gerontology and geriatric medicine at the Sticht Center for Healthy Aging and Alzheimer’s Prevention at Wake Forest University in Winston-Salem, N.C.

It’s “not entirely clear” why greater calorie restriction did not translate to greater vascular benefit, but it “could be related in part to potentially adverse effects of severe CR on vascular function,” she noted. “These findings have important implications for reducing cardiovascular risk with nonpharmacological interventions in high-risk populations.”

Methods and findings

The study included 160 men and women aged 65-79 years, with a body mass index (BMI) of 30 to 45 kg/m². The subjects were randomized to one of three groups for 20 weeks of aerobic exercise only, aerobic exercise plus moderate CR, or aerobic exercise plus more intensive CR. Their exercise regimen involved 30 minutes of supervised treadmill walking for 4 days per week at 65%-70% of heart rate reserve.

Subjects in the moderate CR group decreased caloric intake by 250 kcals a day, while the intense calorie reduction group cut 600 kcals per day. Their meals contained less than 30% of calories from fat and at least 0.8 g of protein per kg of ideal body weight. They were also provided with supplemental calcium (1,200 mg/day) and vitamin D (800 IU/day).

Cardiovascular magnetic resonance imaging was used to assess various aspects of aortic structure and function, including aortic arch pulse wave velocity, aortic distensibility and dimensions, and periaortic fat.

Weight loss was greater among subjects with CR plus exercise, compared with that of patients in the exercise-only group. The degree of weight loss was not significantly different between those with moderate versus intense CR ( 8.02 kg vs. 8.98 kg).

Among the exercise-only group, researchers observed no changes in aortic stiffness. However, adding moderate CR significantly improved this measure, while intense CR did not.

Specifically, subjects in the moderate-CR group had a “robust” 21% increase in distensibility in the descending aorta (DA), and an 8% decrease in aortic arch pulse wave velocity, whereas there were no significant vascular changes in the intense-CR group.

Bests results seen in exercise plus modest CR group

“Collectively, these data suggest that combining exercise with modest CR (as opposed to more intensive CR or no CR) provides the greatest benefit for proximal aortic stiffness, while also optimizing weight loss and improvements in body composition and body fat distribution,” noted the authors in their paper.

“Our data support the growing number of studies indicating that intentional weight loss can be safe for older adults with obesity and extend our previous findings, suggesting that obesity may blunt the beneficial effects of exercise for not only cardiorespiratory fitness, but likely vascular health as well.”

William E. Kraus, MD, professor in the Department of Medicine, Division of Cardiology at Duke University Medical Center, in Durham, NC, described the study as important and interesting for several reasons.

“First, it demonstrates one can change aortic vascular function with a combined diet and exercise program, even in older, obese Americans. This implies it is never too late to make meaningful lifestyle changes that will benefit cardiovascular health,” he said. “Second, it is among an increasing number of studies demonstrating that more is not always better than less in exercise and diet lifestyle changes - and in fact the converse is true.” 

“This gives hope that more people can benefit from modest lifestyle changes - in this case following guidelines for physical activity and only a modest reduction of 250 kilocalories per day resulted in benefit,” Dr. Kraus added.

The authors of the paper and Dr. Kraus disclosed no conflicts of interest.

Small increases in daily physical activity are associated with a boost in 1-year survival in patients with heart failure and coronary disease who received an implantable cardioverter defibrillator (ICD), new research suggests.

“Our study looked at how much exercise was necessary for a better outcome in patients with prior ICD implantation and, for every 10 minutes of exercise, we saw a 1% reduction in the likelihood of death or hospitalization, which is a pretty profound impact on outcome for just a small amount of additional physical activity per day,” lead author Brett Atwater, MD, told this news organization.

“These improvements were achieved outside of a formal cardiac rehabilitation program, suggesting that the benefits of increased physical activity obtained in cardiac rehabilitation programs may also be achievable at home,” he said.

Cardiac rehabilitation (CR) programs have been shown to improve short- and long-term outcomes in patients with heart failure (HF) but continue to be underutilized, especially by women, the elderly, and minorities. Home-based CR could help overcome this limitation but the science behind it is relatively new, noted Dr. Atwater, director of electrophysiology and electrophysiology research, Inova Heart and Vascular Institute, Fairfax, Va.

As reported in Circulation Cardiovascular Quality and Outcomes, the study involved 41,731 Medicare beneficiaries (mean age, 73.5 years) who received an ICD from 2014 to 2016.

ICD heart rate and activity sensor measurements were used to establish a personalized physical activity (PA) threshold for each patient in the first 3 weeks after ICD implantation. Thereafter, the ICD logged PA when the personalized PA threshold was exceeded. The mean baseline PA level was 128.9 minutes/day.

At 3 years’ follow-up, one-quarter of the patients had died and half had been hospitalized for HF. Of the total population, only 3.2% participated in CR.

Compared with nonparticipants, CR participants were more likely to be White (91.0% versus 87.3%), male (75.5% versus 72.2%), and to have diabetes (48.8% versus 44.1%), ischemic heart disease (91.4% versus 82.1%), or congestive heart failure (90.4% versus 83.4%).

CR participants attended a median of 24 sessions, during which time daily PA increased by a mean of 9.7 minutes per day. During the same time, PA decreased by a mean of 1.0 minute per day in non-CR participants (P < .001).

PA levels remained “relatively constant” for the first 36 months of follow-up among CR participants before showing a steep decline, whereas levels gradually declined throughout follow-up among nonparticipants, with a median annual change of –4.5 min/day.

In adjusted analysis, every 10 minutes of increased daily PA was associated with a 1.1% reduced risk for death (hazard ratio, 0.989; 95% confidence interval, 0.979-0.996) and a 1% reduced risk for HF hospitalization (HR, 0.99; 95% CI, 0.986-0.995) at 1-year follow-up (P < .001).

After propensity score was used to match CR participants with nonparticipants by demographic characteristics, comorbidities, and baseline PA level, CR participants had a significantly lower risk for death at 1 year (HR, 0.76; 95% CI, 0.69-0.85). This difference in risk remained at 2- and 3-year follow-ups.

However, when the researchers further adjusted for change in PA during CR or the same time period after device implantation, no differences in mortality were found between CR participants and nonparticipants at 1 year (HR, 1.00; 95% CI, 0.82-1.21) or at 2 or 3 years.

The risk for HF hospitalization did not differ between the two groups in either propensity score model.

Unlike wearable devices, implanted devices “don’t give that type of feedback to patients regarding PA levels – only to providers – and it will be interesting to discover whether providing feedback to patients can motivate them to do more physical activity,” Dr. Atwater commented.

The team is currently enrolling patients in a follow-up trial, in which patients will be given feedback from their ICD “to move these data from an interesting observation to something that can drive outcomes,” he said.

Commenting for this news organization, Melissa Tracy, MD, Rush University Medical Center, Chicago, said the study reiterates the “profound” underutilization of CR.

“Only about 3% of patients who should have qualified for cardiac rehabilitation actually attended, which is startling considering that it has class 1A level of evidence supporting its use,” she said.

Dr. Tracy, who is also a member of the American College of Cardiology’s Prevention of Cardiovascular Disease Section Leadership Council, described the study as “another notch in the belt of positive outcomes supporting the need for cardiac rehabilitation” and emphasizing the importance of a home-based alternative.

“One of the reasons women, minorities, and older patients don’t go to cardiac rehabilitation is they have to get there, rely on someone to drive them, or they have other responsibilities – especially women, who are often primary caretakers of others,” she said. “For women and men, the pressure to get back to work and support their families means they don’t have the luxury to go to cardiac rehabilitation.”

Dr. Tracy noted that home-based CR is covered by CMS until the end of 2021. “An important take-home is for providers and patients to understand that they do have a home-based option,” she stated.

Limitations of the study are that only 24% of patients were women, only 6% were Black, and the results might not be generalizable to patients younger than 65 years, note Dr. Atwater and colleagues. Also, previous implantation might have protected the cohort from experiencing arrhythmic death, and it remains unclear if similar results would be obtained in patients without a previous ICD.

This research was funded through the unrestricted Abbott Medical-Duke Health Strategic Alliance Research Grant. Dr. Atwater receives significant research support from Boston Scientific and Abbott Medical, and modest honoraria from Abbott Medical, Medtronic, and Biotronik. Coauthor disclosures are listed in the paper. Dr. Tracy has created cardiac prevention programs with Virtual Health Partners (VHP) and owns the intellectual property and consults with VHP but receives no monetary compensation.
 

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

Small increases in daily physical activity are associated with a boost in 1-year survival in patients with heart failure and coronary disease who received an implantable cardioverter defibrillator (ICD), new research suggests.

“Our study looked at how much exercise was necessary for a better outcome in patients with prior ICD implantation and, for every 10 minutes of exercise, we saw a 1% reduction in the likelihood of death or hospitalization, which is a pretty profound impact on outcome for just a small amount of additional physical activity per day,” lead author Brett Atwater, MD, told this news organization.

“These improvements were achieved outside of a formal cardiac rehabilitation program, suggesting that the benefits of increased physical activity obtained in cardiac rehabilitation programs may also be achievable at home,” he said.

Cardiac rehabilitation (CR) programs have been shown to improve short- and long-term outcomes in patients with heart failure (HF) but continue to be underutilized, especially by women, the elderly, and minorities. Home-based CR could help overcome this limitation but the science behind it is relatively new, noted Dr. Atwater, director of electrophysiology and electrophysiology research, Inova Heart and Vascular Institute, Fairfax, Va.

As reported in Circulation Cardiovascular Quality and Outcomes, the study involved 41,731 Medicare beneficiaries (mean age, 73.5 years) who received an ICD from 2014 to 2016.

ICD heart rate and activity sensor measurements were used to establish a personalized physical activity (PA) threshold for each patient in the first 3 weeks after ICD implantation. Thereafter, the ICD logged PA when the personalized PA threshold was exceeded. The mean baseline PA level was 128.9 minutes/day.

At 3 years’ follow-up, one-quarter of the patients had died and half had been hospitalized for HF. Of the total population, only 3.2% participated in CR.

Compared with nonparticipants, CR participants were more likely to be White (91.0% versus 87.3%), male (75.5% versus 72.2%), and to have diabetes (48.8% versus 44.1%), ischemic heart disease (91.4% versus 82.1%), or congestive heart failure (90.4% versus 83.4%).

CR participants attended a median of 24 sessions, during which time daily PA increased by a mean of 9.7 minutes per day. During the same time, PA decreased by a mean of 1.0 minute per day in non-CR participants (P < .001).

PA levels remained “relatively constant” for the first 36 months of follow-up among CR participants before showing a steep decline, whereas levels gradually declined throughout follow-up among nonparticipants, with a median annual change of –4.5 min/day.

In adjusted analysis, every 10 minutes of increased daily PA was associated with a 1.1% reduced risk for death (hazard ratio, 0.989; 95% confidence interval, 0.979-0.996) and a 1% reduced risk for HF hospitalization (HR, 0.99; 95% CI, 0.986-0.995) at 1-year follow-up (P < .001).

After propensity score was used to match CR participants with nonparticipants by demographic characteristics, comorbidities, and baseline PA level, CR participants had a significantly lower risk for death at 1 year (HR, 0.76; 95% CI, 0.69-0.85). This difference in risk remained at 2- and 3-year follow-ups.

However, when the researchers further adjusted for change in PA during CR or the same time period after device implantation, no differences in mortality were found between CR participants and nonparticipants at 1 year (HR, 1.00; 95% CI, 0.82-1.21) or at 2 or 3 years.

The risk for HF hospitalization did not differ between the two groups in either propensity score model.

Unlike wearable devices, implanted devices “don’t give that type of feedback to patients regarding PA levels – only to providers – and it will be interesting to discover whether providing feedback to patients can motivate them to do more physical activity,” Dr. Atwater commented.

The team is currently enrolling patients in a follow-up trial, in which patients will be given feedback from their ICD “to move these data from an interesting observation to something that can drive outcomes,” he said.

Commenting for this news organization, Melissa Tracy, MD, Rush University Medical Center, Chicago, said the study reiterates the “profound” underutilization of CR.

“Only about 3% of patients who should have qualified for cardiac rehabilitation actually attended, which is startling considering that it has class 1A level of evidence supporting its use,” she said.

Dr. Tracy, who is also a member of the American College of Cardiology’s Prevention of Cardiovascular Disease Section Leadership Council, described the study as “another notch in the belt of positive outcomes supporting the need for cardiac rehabilitation” and emphasizing the importance of a home-based alternative.

“One of the reasons women, minorities, and older patients don’t go to cardiac rehabilitation is they have to get there, rely on someone to drive them, or they have other responsibilities – especially women, who are often primary caretakers of others,” she said. “For women and men, the pressure to get back to work and support their families means they don’t have the luxury to go to cardiac rehabilitation.”

Dr. Tracy noted that home-based CR is covered by CMS until the end of 2021. “An important take-home is for providers and patients to understand that they do have a home-based option,” she stated.

Limitations of the study are that only 24% of patients were women, only 6% were Black, and the results might not be generalizable to patients younger than 65 years, note Dr. Atwater and colleagues. Also, previous implantation might have protected the cohort from experiencing arrhythmic death, and it remains unclear if similar results would be obtained in patients without a previous ICD.

This research was funded through the unrestricted Abbott Medical-Duke Health Strategic Alliance Research Grant. Dr. Atwater receives significant research support from Boston Scientific and Abbott Medical, and modest honoraria from Abbott Medical, Medtronic, and Biotronik. Coauthor disclosures are listed in the paper. Dr. Tracy has created cardiac prevention programs with Virtual Health Partners (VHP) and owns the intellectual property and consults with VHP but receives no monetary compensation.
 

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

Small increases in daily physical activity are associated with a boost in 1-year survival in patients with heart failure and coronary disease who received an implantable cardioverter defibrillator (ICD), new research suggests.

“Our study looked at how much exercise was necessary for a better outcome in patients with prior ICD implantation and, for every 10 minutes of exercise, we saw a 1% reduction in the likelihood of death or hospitalization, which is a pretty profound impact on outcome for just a small amount of additional physical activity per day,” lead author Brett Atwater, MD, told this news organization.

“These improvements were achieved outside of a formal cardiac rehabilitation program, suggesting that the benefits of increased physical activity obtained in cardiac rehabilitation programs may also be achievable at home,” he said.

Cardiac rehabilitation (CR) programs have been shown to improve short- and long-term outcomes in patients with heart failure (HF) but continue to be underutilized, especially by women, the elderly, and minorities. Home-based CR could help overcome this limitation but the science behind it is relatively new, noted Dr. Atwater, director of electrophysiology and electrophysiology research, Inova Heart and Vascular Institute, Fairfax, Va.

As reported in Circulation Cardiovascular Quality and Outcomes, the study involved 41,731 Medicare beneficiaries (mean age, 73.5 years) who received an ICD from 2014 to 2016.

ICD heart rate and activity sensor measurements were used to establish a personalized physical activity (PA) threshold for each patient in the first 3 weeks after ICD implantation. Thereafter, the ICD logged PA when the personalized PA threshold was exceeded. The mean baseline PA level was 128.9 minutes/day.

At 3 years’ follow-up, one-quarter of the patients had died and half had been hospitalized for HF. Of the total population, only 3.2% participated in CR.

Compared with nonparticipants, CR participants were more likely to be White (91.0% versus 87.3%), male (75.5% versus 72.2%), and to have diabetes (48.8% versus 44.1%), ischemic heart disease (91.4% versus 82.1%), or congestive heart failure (90.4% versus 83.4%).

CR participants attended a median of 24 sessions, during which time daily PA increased by a mean of 9.7 minutes per day. During the same time, PA decreased by a mean of 1.0 minute per day in non-CR participants (P < .001).

PA levels remained “relatively constant” for the first 36 months of follow-up among CR participants before showing a steep decline, whereas levels gradually declined throughout follow-up among nonparticipants, with a median annual change of –4.5 min/day.

In adjusted analysis, every 10 minutes of increased daily PA was associated with a 1.1% reduced risk for death (hazard ratio, 0.989; 95% confidence interval, 0.979-0.996) and a 1% reduced risk for HF hospitalization (HR, 0.99; 95% CI, 0.986-0.995) at 1-year follow-up (P < .001).

After propensity score was used to match CR participants with nonparticipants by demographic characteristics, comorbidities, and baseline PA level, CR participants had a significantly lower risk for death at 1 year (HR, 0.76; 95% CI, 0.69-0.85). This difference in risk remained at 2- and 3-year follow-ups.

However, when the researchers further adjusted for change in PA during CR or the same time period after device implantation, no differences in mortality were found between CR participants and nonparticipants at 1 year (HR, 1.00; 95% CI, 0.82-1.21) or at 2 or 3 years.

The risk for HF hospitalization did not differ between the two groups in either propensity score model.

Unlike wearable devices, implanted devices “don’t give that type of feedback to patients regarding PA levels – only to providers – and it will be interesting to discover whether providing feedback to patients can motivate them to do more physical activity,” Dr. Atwater commented.

The team is currently enrolling patients in a follow-up trial, in which patients will be given feedback from their ICD “to move these data from an interesting observation to something that can drive outcomes,” he said.

Commenting for this news organization, Melissa Tracy, MD, Rush University Medical Center, Chicago, said the study reiterates the “profound” underutilization of CR.

“Only about 3% of patients who should have qualified for cardiac rehabilitation actually attended, which is startling considering that it has class 1A level of evidence supporting its use,” she said.

Dr. Tracy, who is also a member of the American College of Cardiology’s Prevention of Cardiovascular Disease Section Leadership Council, described the study as “another notch in the belt of positive outcomes supporting the need for cardiac rehabilitation” and emphasizing the importance of a home-based alternative.

“One of the reasons women, minorities, and older patients don’t go to cardiac rehabilitation is they have to get there, rely on someone to drive them, or they have other responsibilities – especially women, who are often primary caretakers of others,” she said. “For women and men, the pressure to get back to work and support their families means they don’t have the luxury to go to cardiac rehabilitation.”

Dr. Tracy noted that home-based CR is covered by CMS until the end of 2021. “An important take-home is for providers and patients to understand that they do have a home-based option,” she stated.

Limitations of the study are that only 24% of patients were women, only 6% were Black, and the results might not be generalizable to patients younger than 65 years, note Dr. Atwater and colleagues. Also, previous implantation might have protected the cohort from experiencing arrhythmic death, and it remains unclear if similar results would be obtained in patients without a previous ICD.

This research was funded through the unrestricted Abbott Medical-Duke Health Strategic Alliance Research Grant. Dr. Atwater receives significant research support from Boston Scientific and Abbott Medical, and modest honoraria from Abbott Medical, Medtronic, and Biotronik. Coauthor disclosures are listed in the paper. Dr. Tracy has created cardiac prevention programs with Virtual Health Partners (VHP) and owns the intellectual property and consults with VHP but receives no monetary compensation.
 

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

Since the U.S. Food and Drug Administration established its accelerated drug approval pathway 28 years ago, more than 2 in 5 drugs granted fast-track approval have not been confirmed clinically effective as required, an in-depth investigation published in The BMJ has determined.

“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.

The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
 

Required studies rarely completed

As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.

However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.

The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.

In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.

Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.

For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.

As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.

Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.

“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
 

Call for reform

As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.

In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.

“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.

In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.

Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.

One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.

“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.

An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”

“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.

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

Since the U.S. Food and Drug Administration established its accelerated drug approval pathway 28 years ago, more than 2 in 5 drugs granted fast-track approval have not been confirmed clinically effective as required, an in-depth investigation published in The BMJ has determined.

“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.

The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
 

Required studies rarely completed

As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.

However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.

The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.

In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.

Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.

For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.

As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.

Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.

“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
 

Call for reform

As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.

In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.

“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.

In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.

Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.

One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.

“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.

An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”

“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.

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

Since the U.S. Food and Drug Administration established its accelerated drug approval pathway 28 years ago, more than 2 in 5 drugs granted fast-track approval have not been confirmed clinically effective as required, an in-depth investigation published in The BMJ has determined.

“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.

The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
 

Required studies rarely completed

As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.

However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.

The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.

In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.

Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.

For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.

As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.

Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.

“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
 

Call for reform

As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.

In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.

“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.

In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.

Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.

One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.

“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.

An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”

“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.

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

Newly published data show alarmingly high rates and severity of early diabetes-specific complications in individuals who develop type 2 diabetes at a young age. This suggests intervention should be early and aggressive among these youngsters, said the researchers.

AzmanJaka/E+/Getty Images

The results for the 500 young adult participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth 2 (TODAY 2) study were published online July 29 in the New England Journal of Medicine by the TODAY study group.

At follow-up – after originally participating in the TODAY trial when they were young teenagers – they had a mean age of 26.4 years.

At this time, more than two thirds had hypertension and half had dyslipidemia.

Overall, 60% had at least one diabetic microvascular complication (retinal disease, neuropathy, or diabetic kidney disease), and more than a quarter had two or more such complications.

“These data illustrate the serious personal and public health consequences of youth-onset type 2 diabetes in the transition to adulthood,” the researchers noted.
 

Don’t tread lightly just because they are young

“The fact that these youth are accumulating complications at a rapid rate and are broadly affected early in adulthood certainly suggests that aggressive therapy is needed, both for glycemic control and treatment of risk factors like hypertension and dyslipidemia,” study coauthor Philip S. Zeitler, MD, PhD, said in an interview.

“In the absence of studies specifically addressing this, we need to take a more aggressive approach than people might be inclined to, given that the age at diagnosis is young, around 14 years,” he added.

“Contrary to the inclination to be ‘gentle’ in treating them because they are kids, these data suggest that we can’t let these initial years go by without strong intervention, and we need to be prepared for polypharmacy.”

Unfortunately, as Dr. Zeitler and coauthors explained, youth-onset type 2 diabetes is characterized by a suboptimal response to currently approved diabetes medications.

New pediatric indications in the United States for drugs used to treat type 2 diabetes in adults, including the recent Food and Drug Administration approval of extended-release exenatide for children as young as 10 years of age, “helps, but only marginally,” said Dr. Zeitler, of the Clinical & Translational Research Center, Children’s Hospital Colorado, Aurora.

“In some cases, it will help get them covered by carriers, which is always good. But this is still a very limited set of medications. It doesn’t include more recently approved more potent glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, and doesn’t include the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Pediatricians are used to using medications off label and that is necessary here while we await further approvals,” he said.  

And he noted that most individuals with youth-onset type 2 diabetes in the United States are covered by public insurance or are uninsured, depending on which state they live in. While the two major Medicaid programs in Colorado allow full access to adult formularies, that’s not the case everywhere. Moreover, patients often face further access barriers in states without expanded Medicaid.
 

Follow-up shows all metrics worsening over time

In TODAY 2, patients participated in an observational follow-up in their usual care settings in 2011-2020. At the start, they were receiving metformin with or without insulin for diabetes, but whether this continued and whether they were treated for other risk factors was down to individual circumstances.

Participants’ median A1c increased over time, and the percentage with A1c < 6% (< 48 mmol/mol) declined from 75% at the time of TODAY entry to just 19% at the 15-year end of follow-up.

The proportion with an A1c ≤ 10% (≤ 86 mmol/mol) rose from 0% at baseline to 34% at 15 years.

At that time, nearly 50% were taking both metformin and insulin, while more than a quarter were taking no medications.

The prevalence of hypertension increased from 19.2% at baseline to 67.5% at 15 years, while dyslipidemia rose from 20.8% to 51.6%.

Kidney disease prevalence increased from 8.0% at baseline to 54.8% at 15 years. Nerve disease rose from 1.0% to 32.4%. Retinal disease jumped from 13.7% with milder nonproliferative retinopathy in 2010-2011 to 51.0% with any eye disease in 2017-2018, including 8.8% with moderate to severe retinal changes and 3.5% with macular edema.  

Overall, at the time of the last visit, 39.9% had no diabetes complications, 31.8% had one, 21.3% had two, and 7.1% had three complications.
 

Serious cardiovascular events in mid-20s

There were 17 adjudicated serious cardiovascular events, including four myocardial infarctions, six heart failure events, three diagnoses of coronary artery disease, and four strokes.

Six participants died, one each from myocardial infarction, kidney failure, and drug overdose, and three from sepsis.

Dr. Zeitler called the macrovascular events “shocking,” noting that although the numbers are small, for people in their mid-20s “they should be zero ... While we don’t yet know if the rates are the same or faster than in adults, even if they are the same, these kids are only in their late 20s, as opposed to adults experiencing these problems in their 50s, 60s, and 70s.  

“The fact that these complications are occurring when these individuals should be in the prime of their life for both family and work has huge implications,” he stressed.
 

Findings have multiple causes

The reasons for the findings are both biologic and socioeconomic, Dr. Zeitler said.

“We know already that many kids with type 2 have rapid [deterioration of] beta-cell [function], which is probably very biologic. It stands to reason that an individual who can get diabetes as an adolescent probably has more fragile beta cells in some way,” he noted.

“But we also know that many other things contribute: stress, social determinants, access to quality care and medications, access to healthy foods and physical activity, availability of family supervision given the realities of families’ economic status and jobs, etc.”

It’s also known that youth with type 2 diabetes have much more severe insulin resistance than that of adults with the condition, and that “once the kids left ... the [TODAY] study, risk factor treatment in the community was less than ideal, and a lot of kids who met criteria for treatment of their blood pressure or lipids were not being treated. This is likely at least partly sociologic and partly the general pediatric hesitancy to use medications.”

He said the TODAY team will soon have some new data to show that “glycemia during the early years makes a difference, again supporting intensive intervention early on.”

The TODAY study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler had no further disclosures.

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

Newly published data show alarmingly high rates and severity of early diabetes-specific complications in individuals who develop type 2 diabetes at a young age. This suggests intervention should be early and aggressive among these youngsters, said the researchers.

AzmanJaka/E+/Getty Images

The results for the 500 young adult participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth 2 (TODAY 2) study were published online July 29 in the New England Journal of Medicine by the TODAY study group.

At follow-up – after originally participating in the TODAY trial when they were young teenagers – they had a mean age of 26.4 years.

At this time, more than two thirds had hypertension and half had dyslipidemia.

Overall, 60% had at least one diabetic microvascular complication (retinal disease, neuropathy, or diabetic kidney disease), and more than a quarter had two or more such complications.

“These data illustrate the serious personal and public health consequences of youth-onset type 2 diabetes in the transition to adulthood,” the researchers noted.
 

Don’t tread lightly just because they are young

“The fact that these youth are accumulating complications at a rapid rate and are broadly affected early in adulthood certainly suggests that aggressive therapy is needed, both for glycemic control and treatment of risk factors like hypertension and dyslipidemia,” study coauthor Philip S. Zeitler, MD, PhD, said in an interview.

“In the absence of studies specifically addressing this, we need to take a more aggressive approach than people might be inclined to, given that the age at diagnosis is young, around 14 years,” he added.

“Contrary to the inclination to be ‘gentle’ in treating them because they are kids, these data suggest that we can’t let these initial years go by without strong intervention, and we need to be prepared for polypharmacy.”

Unfortunately, as Dr. Zeitler and coauthors explained, youth-onset type 2 diabetes is characterized by a suboptimal response to currently approved diabetes medications.

New pediatric indications in the United States for drugs used to treat type 2 diabetes in adults, including the recent Food and Drug Administration approval of extended-release exenatide for children as young as 10 years of age, “helps, but only marginally,” said Dr. Zeitler, of the Clinical & Translational Research Center, Children’s Hospital Colorado, Aurora.

“In some cases, it will help get them covered by carriers, which is always good. But this is still a very limited set of medications. It doesn’t include more recently approved more potent glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, and doesn’t include the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Pediatricians are used to using medications off label and that is necessary here while we await further approvals,” he said.  

And he noted that most individuals with youth-onset type 2 diabetes in the United States are covered by public insurance or are uninsured, depending on which state they live in. While the two major Medicaid programs in Colorado allow full access to adult formularies, that’s not the case everywhere. Moreover, patients often face further access barriers in states without expanded Medicaid.
 

Follow-up shows all metrics worsening over time

In TODAY 2, patients participated in an observational follow-up in their usual care settings in 2011-2020. At the start, they were receiving metformin with or without insulin for diabetes, but whether this continued and whether they were treated for other risk factors was down to individual circumstances.

Participants’ median A1c increased over time, and the percentage with A1c < 6% (< 48 mmol/mol) declined from 75% at the time of TODAY entry to just 19% at the 15-year end of follow-up.

The proportion with an A1c ≤ 10% (≤ 86 mmol/mol) rose from 0% at baseline to 34% at 15 years.

At that time, nearly 50% were taking both metformin and insulin, while more than a quarter were taking no medications.

The prevalence of hypertension increased from 19.2% at baseline to 67.5% at 15 years, while dyslipidemia rose from 20.8% to 51.6%.

Kidney disease prevalence increased from 8.0% at baseline to 54.8% at 15 years. Nerve disease rose from 1.0% to 32.4%. Retinal disease jumped from 13.7% with milder nonproliferative retinopathy in 2010-2011 to 51.0% with any eye disease in 2017-2018, including 8.8% with moderate to severe retinal changes and 3.5% with macular edema.  

Overall, at the time of the last visit, 39.9% had no diabetes complications, 31.8% had one, 21.3% had two, and 7.1% had three complications.
 

Serious cardiovascular events in mid-20s

There were 17 adjudicated serious cardiovascular events, including four myocardial infarctions, six heart failure events, three diagnoses of coronary artery disease, and four strokes.

Six participants died, one each from myocardial infarction, kidney failure, and drug overdose, and three from sepsis.

Dr. Zeitler called the macrovascular events “shocking,” noting that although the numbers are small, for people in their mid-20s “they should be zero ... While we don’t yet know if the rates are the same or faster than in adults, even if they are the same, these kids are only in their late 20s, as opposed to adults experiencing these problems in their 50s, 60s, and 70s.  

“The fact that these complications are occurring when these individuals should be in the prime of their life for both family and work has huge implications,” he stressed.
 

Findings have multiple causes

The reasons for the findings are both biologic and socioeconomic, Dr. Zeitler said.

“We know already that many kids with type 2 have rapid [deterioration of] beta-cell [function], which is probably very biologic. It stands to reason that an individual who can get diabetes as an adolescent probably has more fragile beta cells in some way,” he noted.

“But we also know that many other things contribute: stress, social determinants, access to quality care and medications, access to healthy foods and physical activity, availability of family supervision given the realities of families’ economic status and jobs, etc.”

It’s also known that youth with type 2 diabetes have much more severe insulin resistance than that of adults with the condition, and that “once the kids left ... the [TODAY] study, risk factor treatment in the community was less than ideal, and a lot of kids who met criteria for treatment of their blood pressure or lipids were not being treated. This is likely at least partly sociologic and partly the general pediatric hesitancy to use medications.”

He said the TODAY team will soon have some new data to show that “glycemia during the early years makes a difference, again supporting intensive intervention early on.”

The TODAY study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler had no further disclosures.

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

Newly published data show alarmingly high rates and severity of early diabetes-specific complications in individuals who develop type 2 diabetes at a young age. This suggests intervention should be early and aggressive among these youngsters, said the researchers.

AzmanJaka/E+/Getty Images

The results for the 500 young adult participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth 2 (TODAY 2) study were published online July 29 in the New England Journal of Medicine by the TODAY study group.

At follow-up – after originally participating in the TODAY trial when they were young teenagers – they had a mean age of 26.4 years.

At this time, more than two thirds had hypertension and half had dyslipidemia.

Overall, 60% had at least one diabetic microvascular complication (retinal disease, neuropathy, or diabetic kidney disease), and more than a quarter had two or more such complications.

“These data illustrate the serious personal and public health consequences of youth-onset type 2 diabetes in the transition to adulthood,” the researchers noted.
 

Don’t tread lightly just because they are young

“The fact that these youth are accumulating complications at a rapid rate and are broadly affected early in adulthood certainly suggests that aggressive therapy is needed, both for glycemic control and treatment of risk factors like hypertension and dyslipidemia,” study coauthor Philip S. Zeitler, MD, PhD, said in an interview.

“In the absence of studies specifically addressing this, we need to take a more aggressive approach than people might be inclined to, given that the age at diagnosis is young, around 14 years,” he added.

“Contrary to the inclination to be ‘gentle’ in treating them because they are kids, these data suggest that we can’t let these initial years go by without strong intervention, and we need to be prepared for polypharmacy.”

Unfortunately, as Dr. Zeitler and coauthors explained, youth-onset type 2 diabetes is characterized by a suboptimal response to currently approved diabetes medications.

New pediatric indications in the United States for drugs used to treat type 2 diabetes in adults, including the recent Food and Drug Administration approval of extended-release exenatide for children as young as 10 years of age, “helps, but only marginally,” said Dr. Zeitler, of the Clinical & Translational Research Center, Children’s Hospital Colorado, Aurora.

“In some cases, it will help get them covered by carriers, which is always good. But this is still a very limited set of medications. It doesn’t include more recently approved more potent glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, and doesn’t include the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Pediatricians are used to using medications off label and that is necessary here while we await further approvals,” he said.  

And he noted that most individuals with youth-onset type 2 diabetes in the United States are covered by public insurance or are uninsured, depending on which state they live in. While the two major Medicaid programs in Colorado allow full access to adult formularies, that’s not the case everywhere. Moreover, patients often face further access barriers in states without expanded Medicaid.
 

Follow-up shows all metrics worsening over time

In TODAY 2, patients participated in an observational follow-up in their usual care settings in 2011-2020. At the start, they were receiving metformin with or without insulin for diabetes, but whether this continued and whether they were treated for other risk factors was down to individual circumstances.

Participants’ median A1c increased over time, and the percentage with A1c < 6% (< 48 mmol/mol) declined from 75% at the time of TODAY entry to just 19% at the 15-year end of follow-up.

The proportion with an A1c ≤ 10% (≤ 86 mmol/mol) rose from 0% at baseline to 34% at 15 years.

At that time, nearly 50% were taking both metformin and insulin, while more than a quarter were taking no medications.

The prevalence of hypertension increased from 19.2% at baseline to 67.5% at 15 years, while dyslipidemia rose from 20.8% to 51.6%.

Kidney disease prevalence increased from 8.0% at baseline to 54.8% at 15 years. Nerve disease rose from 1.0% to 32.4%. Retinal disease jumped from 13.7% with milder nonproliferative retinopathy in 2010-2011 to 51.0% with any eye disease in 2017-2018, including 8.8% with moderate to severe retinal changes and 3.5% with macular edema.  

Overall, at the time of the last visit, 39.9% had no diabetes complications, 31.8% had one, 21.3% had two, and 7.1% had three complications.
 

Serious cardiovascular events in mid-20s

There were 17 adjudicated serious cardiovascular events, including four myocardial infarctions, six heart failure events, three diagnoses of coronary artery disease, and four strokes.

Six participants died, one each from myocardial infarction, kidney failure, and drug overdose, and three from sepsis.

Dr. Zeitler called the macrovascular events “shocking,” noting that although the numbers are small, for people in their mid-20s “they should be zero ... While we don’t yet know if the rates are the same or faster than in adults, even if they are the same, these kids are only in their late 20s, as opposed to adults experiencing these problems in their 50s, 60s, and 70s.  

“The fact that these complications are occurring when these individuals should be in the prime of their life for both family and work has huge implications,” he stressed.
 

Findings have multiple causes

The reasons for the findings are both biologic and socioeconomic, Dr. Zeitler said.

“We know already that many kids with type 2 have rapid [deterioration of] beta-cell [function], which is probably very biologic. It stands to reason that an individual who can get diabetes as an adolescent probably has more fragile beta cells in some way,” he noted.

“But we also know that many other things contribute: stress, social determinants, access to quality care and medications, access to healthy foods and physical activity, availability of family supervision given the realities of families’ economic status and jobs, etc.”

It’s also known that youth with type 2 diabetes have much more severe insulin resistance than that of adults with the condition, and that “once the kids left ... the [TODAY] study, risk factor treatment in the community was less than ideal, and a lot of kids who met criteria for treatment of their blood pressure or lipids were not being treated. This is likely at least partly sociologic and partly the general pediatric hesitancy to use medications.”

He said the TODAY team will soon have some new data to show that “glycemia during the early years makes a difference, again supporting intensive intervention early on.”

The TODAY study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler had no further disclosures.

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

About one-third of U.S. adults struggled with medical debt during the pandemic, according to data from a Commonwealth Fund survey released July 16.

Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.

The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.

For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.

“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.

“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.

Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.

Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.

“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.

When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.

According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.

George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.

“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”

He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.

“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”

For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.

Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.

“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”

Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.

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

About one-third of U.S. adults struggled with medical debt during the pandemic, according to data from a Commonwealth Fund survey released July 16.

Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.

The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.

For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.

“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.

“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.

Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.

Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.

“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.

When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.

According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.

George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.

“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”

He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.

“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”

For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.

Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.

“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”

Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.

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

About one-third of U.S. adults struggled with medical debt during the pandemic, according to data from a Commonwealth Fund survey released July 16.

Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.

The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.

For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.

“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.

“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.

Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.

Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.

“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.

When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.

According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.

George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.

“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”

He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.

“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”

For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.

Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.

“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”

Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

With COVID, the fun never ends

Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!

sabelskaya/iStock/Getty Images Plus

Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”

Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.

Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.

Joe: Sounds like communism to me, Tony. I’ll say Cuba.

Tony: Sorry Joe, that’s incorrect. Don?

Don: The friends and families sound like freedom-loving Americans, so it must be America.

Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?

Joe: That’s fake news, Tony. It’s gotta be false.

Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.

Don: That’s bulls#&@! I won this thing! I’ll see you in court!
 

More money, more life

Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.

utah778/Thinkstock

Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.

“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.

But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.

We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
 

Holding the ‘health care and wellness’ gun

Cigarettes are not good for us. We know this.

seanika/ThinkStock

It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.

Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.

Philip Morris International is actually leaning hard into nonsmoking means of tobacco consumption, even going so far as to brand itself a “health care and wellness company” on a mission to “unsmoke the world.” And if those aren’t egregious business euphemisms, we don’t know what is.

Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?

So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.

Okay, we lied, it’s the second one.
 

Autopsy of the living dead

Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.

Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.

It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.

Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
 

With COVID, the fun never ends

Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!

sabelskaya/iStock/Getty Images Plus

Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”

Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.

Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.

Joe: Sounds like communism to me, Tony. I’ll say Cuba.

Tony: Sorry Joe, that’s incorrect. Don?

Don: The friends and families sound like freedom-loving Americans, so it must be America.

Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?

Joe: That’s fake news, Tony. It’s gotta be false.

Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.

Don: That’s bulls#&@! I won this thing! I’ll see you in court!
 

More money, more life

Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.

utah778/Thinkstock

Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.

“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.

But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.

We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
 

Holding the ‘health care and wellness’ gun

Cigarettes are not good for us. We know this.

seanika/ThinkStock

It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.

Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.

Philip Morris International is actually leaning hard into nonsmoking means of tobacco consumption, even going so far as to brand itself a “health care and wellness company” on a mission to “unsmoke the world.” And if those aren’t egregious business euphemisms, we don’t know what is.

Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?

So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.

Okay, we lied, it’s the second one.
 

Autopsy of the living dead

Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.

Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.

It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.

Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
 

With COVID, the fun never ends

Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!

sabelskaya/iStock/Getty Images Plus

Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”

Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.

Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.

Joe: Sounds like communism to me, Tony. I’ll say Cuba.

Tony: Sorry Joe, that’s incorrect. Don?

Don: The friends and families sound like freedom-loving Americans, so it must be America.

Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?

Joe: That’s fake news, Tony. It’s gotta be false.

Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.

Don: That’s bulls#&@! I won this thing! I’ll see you in court!
 

More money, more life

Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.

utah778/Thinkstock

Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.

“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.

But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.

We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
 

Holding the ‘health care and wellness’ gun

Cigarettes are not good for us. We know this.

seanika/ThinkStock

It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.

Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.

Philip Morris International is actually leaning hard into nonsmoking means of tobacco consumption, even going so far as to brand itself a “health care and wellness company” on a mission to “unsmoke the world.” And if those aren’t egregious business euphemisms, we don’t know what is.

Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?

So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.

Okay, we lied, it’s the second one.
 

Autopsy of the living dead

Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.

Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.

It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.

Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
 

It’s probably fair to say that most people would like to be thinner. More than 42% of Americans have obesity and another 30% are classified as being overweight, according to the latest statistics from the CDC.

Excess body weight is associated with many illnesses and plays a role in mental health; being heavy can take a toll on self-esteem. Many people worry that carrying excess weight makes them less attractive to potential romantic partners, and both physicians and employers treat those with obesity differently. Furthermore, in psychiatry, many of the medications we prescribe lead to weight gain.

In my clinical practice, I have listened as patients blamed themselves for their body habitus; many won’t consider biological treatments as they feel that would be “cheating” or taking an easy way out. They often point to periods in their life when they did lose weight and believe that they should be able to do it again, even if the weight loss took tremendous effort, was not sustained, and occurred decades ago.

That said, we psychiatrists often find ourselves in the position of managing obesity in our patients. I have been known to give patients who gain weight on antipsychotics either stimulants or metformin, or to add naltrexone to their Wellbutrin (bupropion) to effectively mimic a weight-loss medicine called Contrave. I do think psychiatrists sometimes have an important role in obesity care, an often-overlooked aspect of our profession.
 

Obesity a treatable medical condition

It wasn’t until 2013 that the American Medical Association recognized obesity as a medical condition.

In a New Yorker article that same year, “Diet Drugs Work: Why Won’t Doctors Prescribe Them?” Suzanne Koven wrote: “Several obesity experts told me they’ve encountered doctors who confide that they just didn’t like fat people and don’t enjoy taking care of them. Even doctors who treat obese patients feel stigmatized: ‘diet doctor’ is not a flattering term.”

Eat less, exercise more – with a blame-the-patient attitude – is still what people see as the “right” way to lose weight.

On June 4, 2021, the FDA approved semaglutide, a glucagonlike peptide–1 receptor agonist, previously used for the treatment of diabetes, for use as a weight loss agent for patients with obesity, or for those with a body mass index over 27 kg/m² if they also have a weight-related comorbidity.

Semaglutide has three trade names, all manufactured by Novo Nordisk. The pill version is called Rybelsus and comes in 7-mg and 14-mg tablets. Ozempic is available in 0.5-mg and 1.0-mg doses and is administered weekly by subcutaneous injection for diabetes. The new, higher-dose preparation for weight loss, Wegovy, 2.4 mg, also comes as a weekly subcutaneous dose and is now available for the hefty price of $1,400 per month.

In STEP 1 trials, the higher-dose Wegovy was associated with an average 14.9% weight loss (15.3 kg) over 68 weeks, more than any other single-agent weight loss medication on the market.

GLP-1 receptor agonists work in the brain to decrease appetite, slow gastric emptying, increase insulin secretion, and stimulate brown adipose tissue thermogenesis.
 

Psych drugs lead to weight gain

Elaine Weiner, MD, is the medical director in the outpatient research program of the Maryland Psychiatric Research Center in Catonsville, where she treats patients with schizophrenia.

“Nearly all of our patients gain 20 pounds or more on the combinations of medications we use, mostly atypical antipsychotics,” she said. “Weight management is difficult for people who don’t have problems with motivation, but in our patients, lack of motivation is a core part of their illness, so asking them to adhere to diet and exercise regimens is of limited utility.

“Then, add to that the fact that they sometimes don’t have primary care doctors, and these issues of weight gain and metabolic syndrome come back to the psychiatrist. It is a really bad problem and we need more treatments.”

Fatima Cody Stanford, MD, MPH, MPA,  is a fellowship-trained obesity medicine physician-scientist at the Massachusetts General Hospital Weight Center and Harvard Medical School, both in Boston. She has treated thousands of patients with obesity, speaks internationally on the topic of weight loss medicine, and has published over 100 peer-reviewed articles on obesity.

We spoke at length about recent changes in the field of obesity medicine and the introduction of the new GLP-1 receptor agonists.

“We as physicians have learned so little,” Dr. Stanford said. “This mantra of ‘calories in, calories out’ is not working; this is inaccurate and our focus on this has led to a rise in obesity. All calories are not created the same, and I think we are finally starting to see obesity medicine take off.”

Dr. Stanford is quick to note that obesity is a complex problem. Several different hormones are involved in regulating both appetite and satiety, processed foods promote weight gain, sleep is crucial to weight loss, and exercise helps maintain weight loss but is not usually effective in promoting it. “There are many contributors to energy storage,” she said.

The stimulant phentermine was approved in 1959. Addiction was a concern, and then in the 1990s, it was used in combination with fenfluramine to promote weight loss, a combination known as phen-fen. Fenfluramine was pulled from the market in 1997 when it was found to be associated with pulmonary hypertension and then heart valve abnormalities.

“This frightened quite a few physicians,” Dr. Stanford noted. Phentermine is still used for weight loss, either alone or together with topiramate, as a combination medication called Qsymia, nicknamed phen-top.

“Phen-top is the next best thing we have to semaglutide, and there is an average weight loss of 8%-9% of body weight. Semaglutide is going to be really significant for those people who are responders, and this has been quite well tolerated, the most common side effect being nausea,” she said.

However, she is quick to note that not everyone responds to every medication. “I use each patient’s clinical profile to determine what strategies and which medications to use.”
 

Cardiologists getting in the game

Michael Miller, MD, is a cardiologist at the University of Maryland, Baltimore, and author of “Heal Your Heart” (Emmaus, Pa.: Rodale, 2014). He is very enthusiastic about the approval of semaglutide.

“We are so excited because you finally can use these medicines without having to be diabetic,” Dr. Miller said. “We’re waiting on the results of the SELECT [Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity] trials looking at people who are not diabetic or who are prediabetic, to see the 5-year outcomes with regard to cardiac events.

“Usually endocrinologists prescribe these medications, but cardiologists have started to get into the game since GLP-1 receptor agonists reduce cardiovascular events.” Dr. Miller is hopeful that this medication may neutralize the weight gain caused by psychotropic medications.

Wegovy is administered via weekly injection and, like insulin, is a subcutaneous medication that patients self-administer. Will patients be amenable to injecting a medication for weight loss? Dr. Stanford said that roughly 20%-30% of her patients are hesitant when she suggests that they use liraglutide, another GLP-1 receptor agonist that is approved for weight loss, and some are very fearful of needles.

However, she also noted that during the COVID-19 pandemic, many more patients have sought treatment from obesity medicine physicians because of the association between obesity and mortality from COVID-19. Patients have been willing to consider treatments that they were not previously open to pursuing.

So if people are willing to take Wegovy and doctors are willing to prescribe it, will insurers pay for it? As of this writing, the medication is not yet available, but Ozempic, the lower-dose agent for diabetes, costs $850-$900 for a 4-week supply, according to the GoodRx website.

Liraglutide (Saxenda), the GLP-1 receptor agonist that is currently available for weight loss as a daily injectable, costs $1,300-$1,400 per month.

These medications are not covered by Medicare or Medicaid, and Dr. Stanford, who is well versed as to exactly which private insurers in Massachusetts will and will not reimburse specific medications, said her patients with insurance coverage have been known to delay retirement so that they can remain on the more expensive medications.

“For the past 8 years,” she said, “the Treat and Reduce Obesity Act has had bipartisan support in Congress but has not passed. We are still hopeful that insurers will be required to cover medical and behavioral treatments for obesity.”

As our society struggles to destigmatize so many disorders, obesity remains a highly stigmatized condition, one that our patients cannot hide and one that leads to so many other comorbid illnesses. As new treatments are approved, there will be more for physicians to offer. Semaglutide, if it becomes available to those who need it most, could be a game changer. For patients who have not had success with traditional weight-loss methods, it’s encouraging to have another option available, one that may be reasonable to try before resorting to bariatric surgery.

For decades, psychiatrists have been comfortable prescribing treatments that lead to weight gain. Now, maybe it’s time they also prescribe those that prevent it.

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

It’s probably fair to say that most people would like to be thinner. More than 42% of Americans have obesity and another 30% are classified as being overweight, according to the latest statistics from the CDC.

Excess body weight is associated with many illnesses and plays a role in mental health; being heavy can take a toll on self-esteem. Many people worry that carrying excess weight makes them less attractive to potential romantic partners, and both physicians and employers treat those with obesity differently. Furthermore, in psychiatry, many of the medications we prescribe lead to weight gain.

In my clinical practice, I have listened as patients blamed themselves for their body habitus; many won’t consider biological treatments as they feel that would be “cheating” or taking an easy way out. They often point to periods in their life when they did lose weight and believe that they should be able to do it again, even if the weight loss took tremendous effort, was not sustained, and occurred decades ago.

That said, we psychiatrists often find ourselves in the position of managing obesity in our patients. I have been known to give patients who gain weight on antipsychotics either stimulants or metformin, or to add naltrexone to their Wellbutrin (bupropion) to effectively mimic a weight-loss medicine called Contrave. I do think psychiatrists sometimes have an important role in obesity care, an often-overlooked aspect of our profession.
 

Obesity a treatable medical condition

It wasn’t until 2013 that the American Medical Association recognized obesity as a medical condition.

In a New Yorker article that same year, “Diet Drugs Work: Why Won’t Doctors Prescribe Them?” Suzanne Koven wrote: “Several obesity experts told me they’ve encountered doctors who confide that they just didn’t like fat people and don’t enjoy taking care of them. Even doctors who treat obese patients feel stigmatized: ‘diet doctor’ is not a flattering term.”

Eat less, exercise more – with a blame-the-patient attitude – is still what people see as the “right” way to lose weight.

On June 4, 2021, the FDA approved semaglutide, a glucagonlike peptide–1 receptor agonist, previously used for the treatment of diabetes, for use as a weight loss agent for patients with obesity, or for those with a body mass index over 27 kg/m² if they also have a weight-related comorbidity.

Semaglutide has three trade names, all manufactured by Novo Nordisk. The pill version is called Rybelsus and comes in 7-mg and 14-mg tablets. Ozempic is available in 0.5-mg and 1.0-mg doses and is administered weekly by subcutaneous injection for diabetes. The new, higher-dose preparation for weight loss, Wegovy, 2.4 mg, also comes as a weekly subcutaneous dose and is now available for the hefty price of $1,400 per month.

In STEP 1 trials, the higher-dose Wegovy was associated with an average 14.9% weight loss (15.3 kg) over 68 weeks, more than any other single-agent weight loss medication on the market.

GLP-1 receptor agonists work in the brain to decrease appetite, slow gastric emptying, increase insulin secretion, and stimulate brown adipose tissue thermogenesis.
 

Psych drugs lead to weight gain

Elaine Weiner, MD, is the medical director in the outpatient research program of the Maryland Psychiatric Research Center in Catonsville, where she treats patients with schizophrenia.

“Nearly all of our patients gain 20 pounds or more on the combinations of medications we use, mostly atypical antipsychotics,” she said. “Weight management is difficult for people who don’t have problems with motivation, but in our patients, lack of motivation is a core part of their illness, so asking them to adhere to diet and exercise regimens is of limited utility.

“Then, add to that the fact that they sometimes don’t have primary care doctors, and these issues of weight gain and metabolic syndrome come back to the psychiatrist. It is a really bad problem and we need more treatments.”

Fatima Cody Stanford, MD, MPH, MPA,  is a fellowship-trained obesity medicine physician-scientist at the Massachusetts General Hospital Weight Center and Harvard Medical School, both in Boston. She has treated thousands of patients with obesity, speaks internationally on the topic of weight loss medicine, and has published over 100 peer-reviewed articles on obesity.

We spoke at length about recent changes in the field of obesity medicine and the introduction of the new GLP-1 receptor agonists.

“We as physicians have learned so little,” Dr. Stanford said. “This mantra of ‘calories in, calories out’ is not working; this is inaccurate and our focus on this has led to a rise in obesity. All calories are not created the same, and I think we are finally starting to see obesity medicine take off.”

Dr. Stanford is quick to note that obesity is a complex problem. Several different hormones are involved in regulating both appetite and satiety, processed foods promote weight gain, sleep is crucial to weight loss, and exercise helps maintain weight loss but is not usually effective in promoting it. “There are many contributors to energy storage,” she said.

The stimulant phentermine was approved in 1959. Addiction was a concern, and then in the 1990s, it was used in combination with fenfluramine to promote weight loss, a combination known as phen-fen. Fenfluramine was pulled from the market in 1997 when it was found to be associated with pulmonary hypertension and then heart valve abnormalities.

“This frightened quite a few physicians,” Dr. Stanford noted. Phentermine is still used for weight loss, either alone or together with topiramate, as a combination medication called Qsymia, nicknamed phen-top.

“Phen-top is the next best thing we have to semaglutide, and there is an average weight loss of 8%-9% of body weight. Semaglutide is going to be really significant for those people who are responders, and this has been quite well tolerated, the most common side effect being nausea,” she said.

However, she is quick to note that not everyone responds to every medication. “I use each patient’s clinical profile to determine what strategies and which medications to use.”
 

Cardiologists getting in the game

Michael Miller, MD, is a cardiologist at the University of Maryland, Baltimore, and author of “Heal Your Heart” (Emmaus, Pa.: Rodale, 2014). He is very enthusiastic about the approval of semaglutide.

“We are so excited because you finally can use these medicines without having to be diabetic,” Dr. Miller said. “We’re waiting on the results of the SELECT [Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity] trials looking at people who are not diabetic or who are prediabetic, to see the 5-year outcomes with regard to cardiac events.

“Usually endocrinologists prescribe these medications, but cardiologists have started to get into the game since GLP-1 receptor agonists reduce cardiovascular events.” Dr. Miller is hopeful that this medication may neutralize the weight gain caused by psychotropic medications.

Wegovy is administered via weekly injection and, like insulin, is a subcutaneous medication that patients self-administer. Will patients be amenable to injecting a medication for weight loss? Dr. Stanford said that roughly 20%-30% of her patients are hesitant when she suggests that they use liraglutide, another GLP-1 receptor agonist that is approved for weight loss, and some are very fearful of needles.

However, she also noted that during the COVID-19 pandemic, many more patients have sought treatment from obesity medicine physicians because of the association between obesity and mortality from COVID-19. Patients have been willing to consider treatments that they were not previously open to pursuing.

So if people are willing to take Wegovy and doctors are willing to prescribe it, will insurers pay for it? As of this writing, the medication is not yet available, but Ozempic, the lower-dose agent for diabetes, costs $850-$900 for a 4-week supply, according to the GoodRx website.

Liraglutide (Saxenda), the GLP-1 receptor agonist that is currently available for weight loss as a daily injectable, costs $1,300-$1,400 per month.

These medications are not covered by Medicare or Medicaid, and Dr. Stanford, who is well versed as to exactly which private insurers in Massachusetts will and will not reimburse specific medications, said her patients with insurance coverage have been known to delay retirement so that they can remain on the more expensive medications.

“For the past 8 years,” she said, “the Treat and Reduce Obesity Act has had bipartisan support in Congress but has not passed. We are still hopeful that insurers will be required to cover medical and behavioral treatments for obesity.”

As our society struggles to destigmatize so many disorders, obesity remains a highly stigmatized condition, one that our patients cannot hide and one that leads to so many other comorbid illnesses. As new treatments are approved, there will be more for physicians to offer. Semaglutide, if it becomes available to those who need it most, could be a game changer. For patients who have not had success with traditional weight-loss methods, it’s encouraging to have another option available, one that may be reasonable to try before resorting to bariatric surgery.

For decades, psychiatrists have been comfortable prescribing treatments that lead to weight gain. Now, maybe it’s time they also prescribe those that prevent it.

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

It’s probably fair to say that most people would like to be thinner. More than 42% of Americans have obesity and another 30% are classified as being overweight, according to the latest statistics from the CDC.

Excess body weight is associated with many illnesses and plays a role in mental health; being heavy can take a toll on self-esteem. Many people worry that carrying excess weight makes them less attractive to potential romantic partners, and both physicians and employers treat those with obesity differently. Furthermore, in psychiatry, many of the medications we prescribe lead to weight gain.

In my clinical practice, I have listened as patients blamed themselves for their body habitus; many won’t consider biological treatments as they feel that would be “cheating” or taking an easy way out. They often point to periods in their life when they did lose weight and believe that they should be able to do it again, even if the weight loss took tremendous effort, was not sustained, and occurred decades ago.

That said, we psychiatrists often find ourselves in the position of managing obesity in our patients. I have been known to give patients who gain weight on antipsychotics either stimulants or metformin, or to add naltrexone to their Wellbutrin (bupropion) to effectively mimic a weight-loss medicine called Contrave. I do think psychiatrists sometimes have an important role in obesity care, an often-overlooked aspect of our profession.
 

Obesity a treatable medical condition

It wasn’t until 2013 that the American Medical Association recognized obesity as a medical condition.

In a New Yorker article that same year, “Diet Drugs Work: Why Won’t Doctors Prescribe Them?” Suzanne Koven wrote: “Several obesity experts told me they’ve encountered doctors who confide that they just didn’t like fat people and don’t enjoy taking care of them. Even doctors who treat obese patients feel stigmatized: ‘diet doctor’ is not a flattering term.”

Eat less, exercise more – with a blame-the-patient attitude – is still what people see as the “right” way to lose weight.

On June 4, 2021, the FDA approved semaglutide, a glucagonlike peptide–1 receptor agonist, previously used for the treatment of diabetes, for use as a weight loss agent for patients with obesity, or for those with a body mass index over 27 kg/m² if they also have a weight-related comorbidity.

Semaglutide has three trade names, all manufactured by Novo Nordisk. The pill version is called Rybelsus and comes in 7-mg and 14-mg tablets. Ozempic is available in 0.5-mg and 1.0-mg doses and is administered weekly by subcutaneous injection for diabetes. The new, higher-dose preparation for weight loss, Wegovy, 2.4 mg, also comes as a weekly subcutaneous dose and is now available for the hefty price of $1,400 per month.

In STEP 1 trials, the higher-dose Wegovy was associated with an average 14.9% weight loss (15.3 kg) over 68 weeks, more than any other single-agent weight loss medication on the market.

GLP-1 receptor agonists work in the brain to decrease appetite, slow gastric emptying, increase insulin secretion, and stimulate brown adipose tissue thermogenesis.
 

Psych drugs lead to weight gain

Elaine Weiner, MD, is the medical director in the outpatient research program of the Maryland Psychiatric Research Center in Catonsville, where she treats patients with schizophrenia.

“Nearly all of our patients gain 20 pounds or more on the combinations of medications we use, mostly atypical antipsychotics,” she said. “Weight management is difficult for people who don’t have problems with motivation, but in our patients, lack of motivation is a core part of their illness, so asking them to adhere to diet and exercise regimens is of limited utility.

“Then, add to that the fact that they sometimes don’t have primary care doctors, and these issues of weight gain and metabolic syndrome come back to the psychiatrist. It is a really bad problem and we need more treatments.”

Fatima Cody Stanford, MD, MPH, MPA,  is a fellowship-trained obesity medicine physician-scientist at the Massachusetts General Hospital Weight Center and Harvard Medical School, both in Boston. She has treated thousands of patients with obesity, speaks internationally on the topic of weight loss medicine, and has published over 100 peer-reviewed articles on obesity.

We spoke at length about recent changes in the field of obesity medicine and the introduction of the new GLP-1 receptor agonists.

“We as physicians have learned so little,” Dr. Stanford said. “This mantra of ‘calories in, calories out’ is not working; this is inaccurate and our focus on this has led to a rise in obesity. All calories are not created the same, and I think we are finally starting to see obesity medicine take off.”

Dr. Stanford is quick to note that obesity is a complex problem. Several different hormones are involved in regulating both appetite and satiety, processed foods promote weight gain, sleep is crucial to weight loss, and exercise helps maintain weight loss but is not usually effective in promoting it. “There are many contributors to energy storage,” she said.

The stimulant phentermine was approved in 1959. Addiction was a concern, and then in the 1990s, it was used in combination with fenfluramine to promote weight loss, a combination known as phen-fen. Fenfluramine was pulled from the market in 1997 when it was found to be associated with pulmonary hypertension and then heart valve abnormalities.

“This frightened quite a few physicians,” Dr. Stanford noted. Phentermine is still used for weight loss, either alone or together with topiramate, as a combination medication called Qsymia, nicknamed phen-top.

“Phen-top is the next best thing we have to semaglutide, and there is an average weight loss of 8%-9% of body weight. Semaglutide is going to be really significant for those people who are responders, and this has been quite well tolerated, the most common side effect being nausea,” she said.

However, she is quick to note that not everyone responds to every medication. “I use each patient’s clinical profile to determine what strategies and which medications to use.”
 

Cardiologists getting in the game

Michael Miller, MD, is a cardiologist at the University of Maryland, Baltimore, and author of “Heal Your Heart” (Emmaus, Pa.: Rodale, 2014). He is very enthusiastic about the approval of semaglutide.

“We are so excited because you finally can use these medicines without having to be diabetic,” Dr. Miller said. “We’re waiting on the results of the SELECT [Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity] trials looking at people who are not diabetic or who are prediabetic, to see the 5-year outcomes with regard to cardiac events.

“Usually endocrinologists prescribe these medications, but cardiologists have started to get into the game since GLP-1 receptor agonists reduce cardiovascular events.” Dr. Miller is hopeful that this medication may neutralize the weight gain caused by psychotropic medications.

Wegovy is administered via weekly injection and, like insulin, is a subcutaneous medication that patients self-administer. Will patients be amenable to injecting a medication for weight loss? Dr. Stanford said that roughly 20%-30% of her patients are hesitant when she suggests that they use liraglutide, another GLP-1 receptor agonist that is approved for weight loss, and some are very fearful of needles.

However, she also noted that during the COVID-19 pandemic, many more patients have sought treatment from obesity medicine physicians because of the association between obesity and mortality from COVID-19. Patients have been willing to consider treatments that they were not previously open to pursuing.

So if people are willing to take Wegovy and doctors are willing to prescribe it, will insurers pay for it? As of this writing, the medication is not yet available, but Ozempic, the lower-dose agent for diabetes, costs $850-$900 for a 4-week supply, according to the GoodRx website.

Liraglutide (Saxenda), the GLP-1 receptor agonist that is currently available for weight loss as a daily injectable, costs $1,300-$1,400 per month.

These medications are not covered by Medicare or Medicaid, and Dr. Stanford, who is well versed as to exactly which private insurers in Massachusetts will and will not reimburse specific medications, said her patients with insurance coverage have been known to delay retirement so that they can remain on the more expensive medications.

“For the past 8 years,” she said, “the Treat and Reduce Obesity Act has had bipartisan support in Congress but has not passed. We are still hopeful that insurers will be required to cover medical and behavioral treatments for obesity.”

As our society struggles to destigmatize so many disorders, obesity remains a highly stigmatized condition, one that our patients cannot hide and one that leads to so many other comorbid illnesses. As new treatments are approved, there will be more for physicians to offer. Semaglutide, if it becomes available to those who need it most, could be a game changer. For patients who have not had success with traditional weight-loss methods, it’s encouraging to have another option available, one that may be reasonable to try before resorting to bariatric surgery.

For decades, psychiatrists have been comfortable prescribing treatments that lead to weight gain. Now, maybe it’s time they also prescribe those that prevent it.

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

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

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

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

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

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

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