Key clinical point: The findings from the C-Cubed study support the extension of sequential treatment (fluoropyrimidines with bevacizumab followed by oxaliplatin at first progression) over combination treatment (fluoropyrimidines and oxaliplatin with bevacizumab) in selected patients with previously untreated metastatic colorectal cancer (mCRC) who do not need an objective response.

Major finding: Sequential vs combination treatment led to a significantly longer time to failure of strategy (15.2 vs 7.8 months; hazard ratio 0.49; P < .0001). However, the median overall survival (P = .61) or time between randomization and the first progressive disease (P = .12) was not significantly different between the treatment groups.

Study details: Findings are from a phase 3 trial, C-Cubed Study, which included 300 patients aged ≥20 years with previously untreated mCRC who were randomly assigned to receive sequential (n = 151) or combination (n = 149) treatment.

Disclosures: The study was sponsored by Chugai Pharmaceutical, Co., Ltd. Some authors reported receiving grants or personal fees from various sources, including Chugai Pharmaceutical.

Source: Inada R et al. Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study. Eur J Cancer. 2022;169:166-178 (May 12). Doi: 10.1016/j.ejca.2022.04.009

Key clinical point: The findings from the C-Cubed study support the extension of sequential treatment (fluoropyrimidines with bevacizumab followed by oxaliplatin at first progression) over combination treatment (fluoropyrimidines and oxaliplatin with bevacizumab) in selected patients with previously untreated metastatic colorectal cancer (mCRC) who do not need an objective response.

Major finding: Sequential vs combination treatment led to a significantly longer time to failure of strategy (15.2 vs 7.8 months; hazard ratio 0.49; P < .0001). However, the median overall survival (P = .61) or time between randomization and the first progressive disease (P = .12) was not significantly different between the treatment groups.

Study details: Findings are from a phase 3 trial, C-Cubed Study, which included 300 patients aged ≥20 years with previously untreated mCRC who were randomly assigned to receive sequential (n = 151) or combination (n = 149) treatment.

Disclosures: The study was sponsored by Chugai Pharmaceutical, Co., Ltd. Some authors reported receiving grants or personal fees from various sources, including Chugai Pharmaceutical.

Source: Inada R et al. Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study. Eur J Cancer. 2022;169:166-178 (May 12). Doi: 10.1016/j.ejca.2022.04.009

Key clinical point: The findings from the C-Cubed study support the extension of sequential treatment (fluoropyrimidines with bevacizumab followed by oxaliplatin at first progression) over combination treatment (fluoropyrimidines and oxaliplatin with bevacizumab) in selected patients with previously untreated metastatic colorectal cancer (mCRC) who do not need an objective response.

Major finding: Sequential vs combination treatment led to a significantly longer time to failure of strategy (15.2 vs 7.8 months; hazard ratio 0.49; P < .0001). However, the median overall survival (P = .61) or time between randomization and the first progressive disease (P = .12) was not significantly different between the treatment groups.

Study details: Findings are from a phase 3 trial, C-Cubed Study, which included 300 patients aged ≥20 years with previously untreated mCRC who were randomly assigned to receive sequential (n = 151) or combination (n = 149) treatment.

Disclosures: The study was sponsored by Chugai Pharmaceutical, Co., Ltd. Some authors reported receiving grants or personal fees from various sources, including Chugai Pharmaceutical.

Source: Inada R et al. Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study. Eur J Cancer. 2022;169:166-178 (May 12). Doi: 10.1016/j.ejca.2022.04.009

Not all patients with chronic obstructive pulmonary disease (COPD) respond equally well to pulmonary rehabilitation (PR).

Now, physicians can better categorize which patients will do well with PR and which ones less well or not well at all based on a new system of clustering of COPD patients according to their response to exercise therapy.

“We identified four clusters of COPD patients and their response to PR in the aim to better understand PR outcome and [adapt] it to patients’ profiles and needs,” lead author Yara Al Chikhanie, MD, of the cardiopulmonary rehabilitation center Dieulefit Sante (France), and colleagues observed.

“Identification of patients likely to show smaller responses to PR may help to target patients benefiting the most and to adapt PR settings for nonresponders to standard PR,” they suggested.

The study was published online in Respiratory Medicine.

Single-center cohort

The cohort consisted of 835 patients from a single center who had been admitted to a cardiopulmonary rehabilitation center over a 6-year period from 2021 to 2017. “The PR program used in the center was the same over the 6-year period,” the authors note – consisting of a 3- to 4-week, inpatient program with activities 5 days a week.

Each day, patients attended a 25-minute aerobic training session on a cycling ergometer or a treadmill; a 30-minute low-intensity gym session; a 30-minute group walk outdoors, and 30 minutes of strength training. “We aimed to cluster patients with COPD admitted to PR based on patients’ clinical characteristics and 6-meter walk test results (6MWT), pulse oxygen saturation (SPO₂), heart rate (HR), and dyspnea,” the authors explained.

They then evaluated patient response to PR in each of these clusters based on the amount of improvement in the 6-meter walk distance (6MWD), lung function, and quality of life observed, they added.

The population consisted of seniors, equally men and women, mostly GOLD II and III patients (a measure of lung function) with a limited walking capacity, some 84% of the cohort having a 6MWD <80% predicted. The characteristics of the four identified clusters were as follows:

• Cluster 1: Consisted of younger men, GOLD I to II, average walkers, obese. The average 6MWD was 430 meters and patients had a large exercise HR response to PR. This cluster had a 76 meter improvement in their 6MWD, although 16% of the same cluster still did not respond to PR.
• Cluster 2: Consisted of older women, GOLD II-III, who were slow walkers. This cluster had a reduced 6MWD of 362 meters, but they also had a significant 97-meter improvement in their 6MWD following PR. Some 18% were still nonresponders to PR.
• Cluster 3: Consisted of older men, GOLD II to III, dyspneic, slow walkers, some 32% of whom responded to PR. This cluster also had a reduced 6MWD at 388 meters, but again, they also had a significant improvement of 79 meters in their 6MWD following the introduction of PR. Some 11% were nonresponders to PR.
• Cluster 4: Consisted of older men, GOLD III to IV, very slow walkers, oxygen-dependent, very dyspneic. This cluster had a severely reduced 6MWD of only 290 meters with severe exercise desaturation and dyspnea, and almost all of them were on long-term oxygen therapy. Nevertheless, this cluster also had a significant, 66-meter improvement in their 6MWD. Twenty-eight percent of them were nonresponders to PR.

Clinical practice

“The highly heterogeneous nature of the enrolled patient population reflects clinical practice,” the authors point out. For example, cluster 1 included patients with the best lung function, compared with those in clusters 2, 3, and 4 – which may be due, at least in part, to the aggravation in disease severity with age given that patients in cluster 1 were the youngest overall.

The fact that those in cluster 4 had the worst performance may also have been because of age and disease severity, the authors note, as those in cluster 4 had the highest proportion of patients on long-term oxygen therapy, again suggestive of disease severity. “Of note, these patients show the most impaired 6MWT responses despite the use of oxygen supplementation during walking,” the researchers added.

The authors also suggest that patients such as those in cluster 4 may require specific PR modalities in order to optimize their functional benefits. In contrast, those in cluster 1 had a significantly higher body mass index, compared with those in the other 3 clusters, which, interestingly enough, was not associated with more severe functional exercise impairment. The fact that older age participants, such as those in cluster 3 as well as those with high BMI in cluster 1, were both able to improve their 6MWD post-PR to the same extent as younger patients without obesity suggests that most older or overweight/obese patients can still show clinically significant improvement in 6MWD post PR, as the authors suggest.

Notably, the 6MWT was the only test available both pre-and post PR, making this an important limitation of the study, because only one aspect of the effect of PR was evaluated, omitting other physical and psychosocial benefits of PR, investigators suggest.

Adds to the literature

Asked to comment on the findings, Sachin Gupta, MD, attending physician, pulmonary & critical care medicine, Alameda Health System, Highland Hospital, Oakland, Calif., felt that these data add to the literature in defining COPD patient profiles, helping to categorize those in whom to expect greater walk distance improvements with PR versus those who will respond less well.

“Because 6MWD is a surrogate marker for quality of life (QOL) and mortality, further analysis in the form of a randomized controlled trial to determine long-term outcomes among the four clusters with adjustment for baseline characteristics would help determine the extent to which certain patient clusters may respond to PR,” Dr. Gupta told this news organization in an email.

At the same time, he suggested that while patients may not experience much net benefit in their 6MWD, their QOL or mortality risk may still improve with PR. “I cannot recall a patient ever describing their experience with PR as anything other than positive,” Dr. Gupta stressed.

“And as the authors [themselves] note, because PR serves to benefit patients beyond the 6MWD, I would not recommend limiting PR referrals based on the patient clusters identified,” he said.

The authors had no conflicts of interest to declare. Dr. Gupta declared that he is an employee and shareholder at Genentech.

Not all patients with chronic obstructive pulmonary disease (COPD) respond equally well to pulmonary rehabilitation (PR).

Now, physicians can better categorize which patients will do well with PR and which ones less well or not well at all based on a new system of clustering of COPD patients according to their response to exercise therapy.

“We identified four clusters of COPD patients and their response to PR in the aim to better understand PR outcome and [adapt] it to patients’ profiles and needs,” lead author Yara Al Chikhanie, MD, of the cardiopulmonary rehabilitation center Dieulefit Sante (France), and colleagues observed.

“Identification of patients likely to show smaller responses to PR may help to target patients benefiting the most and to adapt PR settings for nonresponders to standard PR,” they suggested.

The study was published online in Respiratory Medicine.

Single-center cohort

The cohort consisted of 835 patients from a single center who had been admitted to a cardiopulmonary rehabilitation center over a 6-year period from 2021 to 2017. “The PR program used in the center was the same over the 6-year period,” the authors note – consisting of a 3- to 4-week, inpatient program with activities 5 days a week.

Each day, patients attended a 25-minute aerobic training session on a cycling ergometer or a treadmill; a 30-minute low-intensity gym session; a 30-minute group walk outdoors, and 30 minutes of strength training. “We aimed to cluster patients with COPD admitted to PR based on patients’ clinical characteristics and 6-meter walk test results (6MWT), pulse oxygen saturation (SPO₂), heart rate (HR), and dyspnea,” the authors explained.

They then evaluated patient response to PR in each of these clusters based on the amount of improvement in the 6-meter walk distance (6MWD), lung function, and quality of life observed, they added.

The population consisted of seniors, equally men and women, mostly GOLD II and III patients (a measure of lung function) with a limited walking capacity, some 84% of the cohort having a 6MWD <80% predicted. The characteristics of the four identified clusters were as follows:

• Cluster 1: Consisted of younger men, GOLD I to II, average walkers, obese. The average 6MWD was 430 meters and patients had a large exercise HR response to PR. This cluster had a 76 meter improvement in their 6MWD, although 16% of the same cluster still did not respond to PR.
• Cluster 2: Consisted of older women, GOLD II-III, who were slow walkers. This cluster had a reduced 6MWD of 362 meters, but they also had a significant 97-meter improvement in their 6MWD following PR. Some 18% were still nonresponders to PR.
• Cluster 3: Consisted of older men, GOLD II to III, dyspneic, slow walkers, some 32% of whom responded to PR. This cluster also had a reduced 6MWD at 388 meters, but again, they also had a significant improvement of 79 meters in their 6MWD following the introduction of PR. Some 11% were nonresponders to PR.
• Cluster 4: Consisted of older men, GOLD III to IV, very slow walkers, oxygen-dependent, very dyspneic. This cluster had a severely reduced 6MWD of only 290 meters with severe exercise desaturation and dyspnea, and almost all of them were on long-term oxygen therapy. Nevertheless, this cluster also had a significant, 66-meter improvement in their 6MWD. Twenty-eight percent of them were nonresponders to PR.

Clinical practice

“The highly heterogeneous nature of the enrolled patient population reflects clinical practice,” the authors point out. For example, cluster 1 included patients with the best lung function, compared with those in clusters 2, 3, and 4 – which may be due, at least in part, to the aggravation in disease severity with age given that patients in cluster 1 were the youngest overall.

The fact that those in cluster 4 had the worst performance may also have been because of age and disease severity, the authors note, as those in cluster 4 had the highest proportion of patients on long-term oxygen therapy, again suggestive of disease severity. “Of note, these patients show the most impaired 6MWT responses despite the use of oxygen supplementation during walking,” the researchers added.

The authors also suggest that patients such as those in cluster 4 may require specific PR modalities in order to optimize their functional benefits. In contrast, those in cluster 1 had a significantly higher body mass index, compared with those in the other 3 clusters, which, interestingly enough, was not associated with more severe functional exercise impairment. The fact that older age participants, such as those in cluster 3 as well as those with high BMI in cluster 1, were both able to improve their 6MWD post-PR to the same extent as younger patients without obesity suggests that most older or overweight/obese patients can still show clinically significant improvement in 6MWD post PR, as the authors suggest.

Notably, the 6MWT was the only test available both pre-and post PR, making this an important limitation of the study, because only one aspect of the effect of PR was evaluated, omitting other physical and psychosocial benefits of PR, investigators suggest.

Adds to the literature

Asked to comment on the findings, Sachin Gupta, MD, attending physician, pulmonary & critical care medicine, Alameda Health System, Highland Hospital, Oakland, Calif., felt that these data add to the literature in defining COPD patient profiles, helping to categorize those in whom to expect greater walk distance improvements with PR versus those who will respond less well.

“Because 6MWD is a surrogate marker for quality of life (QOL) and mortality, further analysis in the form of a randomized controlled trial to determine long-term outcomes among the four clusters with adjustment for baseline characteristics would help determine the extent to which certain patient clusters may respond to PR,” Dr. Gupta told this news organization in an email.

At the same time, he suggested that while patients may not experience much net benefit in their 6MWD, their QOL or mortality risk may still improve with PR. “I cannot recall a patient ever describing their experience with PR as anything other than positive,” Dr. Gupta stressed.

“And as the authors [themselves] note, because PR serves to benefit patients beyond the 6MWD, I would not recommend limiting PR referrals based on the patient clusters identified,” he said.

The authors had no conflicts of interest to declare. Dr. Gupta declared that he is an employee and shareholder at Genentech.

Not all patients with chronic obstructive pulmonary disease (COPD) respond equally well to pulmonary rehabilitation (PR).

Now, physicians can better categorize which patients will do well with PR and which ones less well or not well at all based on a new system of clustering of COPD patients according to their response to exercise therapy.

“We identified four clusters of COPD patients and their response to PR in the aim to better understand PR outcome and [adapt] it to patients’ profiles and needs,” lead author Yara Al Chikhanie, MD, of the cardiopulmonary rehabilitation center Dieulefit Sante (France), and colleagues observed.

“Identification of patients likely to show smaller responses to PR may help to target patients benefiting the most and to adapt PR settings for nonresponders to standard PR,” they suggested.

The study was published online in Respiratory Medicine.

Single-center cohort

The cohort consisted of 835 patients from a single center who had been admitted to a cardiopulmonary rehabilitation center over a 6-year period from 2021 to 2017. “The PR program used in the center was the same over the 6-year period,” the authors note – consisting of a 3- to 4-week, inpatient program with activities 5 days a week.

Each day, patients attended a 25-minute aerobic training session on a cycling ergometer or a treadmill; a 30-minute low-intensity gym session; a 30-minute group walk outdoors, and 30 minutes of strength training. “We aimed to cluster patients with COPD admitted to PR based on patients’ clinical characteristics and 6-meter walk test results (6MWT), pulse oxygen saturation (SPO₂), heart rate (HR), and dyspnea,” the authors explained.

They then evaluated patient response to PR in each of these clusters based on the amount of improvement in the 6-meter walk distance (6MWD), lung function, and quality of life observed, they added.

The population consisted of seniors, equally men and women, mostly GOLD II and III patients (a measure of lung function) with a limited walking capacity, some 84% of the cohort having a 6MWD <80% predicted. The characteristics of the four identified clusters were as follows:

• Cluster 1: Consisted of younger men, GOLD I to II, average walkers, obese. The average 6MWD was 430 meters and patients had a large exercise HR response to PR. This cluster had a 76 meter improvement in their 6MWD, although 16% of the same cluster still did not respond to PR.
• Cluster 2: Consisted of older women, GOLD II-III, who were slow walkers. This cluster had a reduced 6MWD of 362 meters, but they also had a significant 97-meter improvement in their 6MWD following PR. Some 18% were still nonresponders to PR.
• Cluster 3: Consisted of older men, GOLD II to III, dyspneic, slow walkers, some 32% of whom responded to PR. This cluster also had a reduced 6MWD at 388 meters, but again, they also had a significant improvement of 79 meters in their 6MWD following the introduction of PR. Some 11% were nonresponders to PR.
• Cluster 4: Consisted of older men, GOLD III to IV, very slow walkers, oxygen-dependent, very dyspneic. This cluster had a severely reduced 6MWD of only 290 meters with severe exercise desaturation and dyspnea, and almost all of them were on long-term oxygen therapy. Nevertheless, this cluster also had a significant, 66-meter improvement in their 6MWD. Twenty-eight percent of them were nonresponders to PR.

Clinical practice

“The highly heterogeneous nature of the enrolled patient population reflects clinical practice,” the authors point out. For example, cluster 1 included patients with the best lung function, compared with those in clusters 2, 3, and 4 – which may be due, at least in part, to the aggravation in disease severity with age given that patients in cluster 1 were the youngest overall.

The fact that those in cluster 4 had the worst performance may also have been because of age and disease severity, the authors note, as those in cluster 4 had the highest proportion of patients on long-term oxygen therapy, again suggestive of disease severity. “Of note, these patients show the most impaired 6MWT responses despite the use of oxygen supplementation during walking,” the researchers added.

The authors also suggest that patients such as those in cluster 4 may require specific PR modalities in order to optimize their functional benefits. In contrast, those in cluster 1 had a significantly higher body mass index, compared with those in the other 3 clusters, which, interestingly enough, was not associated with more severe functional exercise impairment. The fact that older age participants, such as those in cluster 3 as well as those with high BMI in cluster 1, were both able to improve their 6MWD post-PR to the same extent as younger patients without obesity suggests that most older or overweight/obese patients can still show clinically significant improvement in 6MWD post PR, as the authors suggest.

Notably, the 6MWT was the only test available both pre-and post PR, making this an important limitation of the study, because only one aspect of the effect of PR was evaluated, omitting other physical and psychosocial benefits of PR, investigators suggest.

Adds to the literature

Asked to comment on the findings, Sachin Gupta, MD, attending physician, pulmonary & critical care medicine, Alameda Health System, Highland Hospital, Oakland, Calif., felt that these data add to the literature in defining COPD patient profiles, helping to categorize those in whom to expect greater walk distance improvements with PR versus those who will respond less well.

“Because 6MWD is a surrogate marker for quality of life (QOL) and mortality, further analysis in the form of a randomized controlled trial to determine long-term outcomes among the four clusters with adjustment for baseline characteristics would help determine the extent to which certain patient clusters may respond to PR,” Dr. Gupta told this news organization in an email.

At the same time, he suggested that while patients may not experience much net benefit in their 6MWD, their QOL or mortality risk may still improve with PR. “I cannot recall a patient ever describing their experience with PR as anything other than positive,” Dr. Gupta stressed.

“And as the authors [themselves] note, because PR serves to benefit patients beyond the 6MWD, I would not recommend limiting PR referrals based on the patient clusters identified,” he said.

The authors had no conflicts of interest to declare. Dr. Gupta declared that he is an employee and shareholder at Genentech.

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Breastfeeding duration is associated with improved cognitive scores at ages 5-14, even after controlling for maternal socioeconomic position and cognitive ability, said the researchers behind a new study.

Despite previous studies demonstrating an association between breastfeeding and standardized intelligence test scores – with breastfed infants scoring higher on intelligence tests than non-breastfed infants – a causal relationship is still contested.

“There is some debate about whether breastfeeding a baby for a longer period of time improves their cognitive development,” the authors of the new study said. They went on to explain how improved cognitive outcomes in breastfed infants could potentially be explained by other characteristics of the women, such as “socioeconomics and maternal intelligence.”
 

Important at the population level

For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford (England) set out to investigate how much these confounders influenced the association between breastfeeding duration and cognitive development.

They analyzed data from the U.K. Millennium Cohort Study on 7,855 infants born in 2000 to 2002 and followed until age 14. They highlighted that although the cohort was not specifically designed to address the association between breastfeeding and cognition, it included information on duration of any breastfeeding, duration of exclusive breastfeeding, verbal cognitive scores at ages 5, 7, 11, and 14, spatial cognitive scores at ages 5, 7, and 11, as well as potential confounders, including socioeconomic characteristics and maternal cognition, based on a vocabulary test.

The researchers discovered that longer breastfeeding durations were associated with higher verbal and spatial cognitive scores at all ages up to 14 and 11, respectively.

After taking the differences in socioeconomic position and maternal cognitive ability into account, those children who were breastfed for longer scored higher in cognitive measures up to age 14, compared with children who were not breastfed. They also found that longer breastfeeding durations were associated with mean cognitive scores 0.08-0.26 standard deviations higher than the mean cognitive score of those who were never breastfed. “This difference may seem small for an individual child but could be important at the population level,” the authors commented.
 

Modest effect

In the United Kingdom, women who have more educational qualifications and are more economically advantaged tend to breastfeed for longer, said the authors. In addition, they added, this group tends to “score more highly on cognitive tests.”

These differences could explain why babies who breastfeed for longer do better in cognitive assessments. However, they said that in their study, “we found that even after taking these differences into account, children breastfed for longer scored higher in cognitive measures up to age 14, in comparison to children who were not breastfed.”

The authors explained that the association between breastfeeding duration and cognitive scores “persists after adjusting for socioeconomics and maternal intelligence.” However, they pointed out that “the effect was modest.”

A version of this article first appeared on Medscape UK.

Breastfeeding duration is associated with improved cognitive scores at ages 5-14, even after controlling for maternal socioeconomic position and cognitive ability, said the researchers behind a new study.

Despite previous studies demonstrating an association between breastfeeding and standardized intelligence test scores – with breastfed infants scoring higher on intelligence tests than non-breastfed infants – a causal relationship is still contested.

“There is some debate about whether breastfeeding a baby for a longer period of time improves their cognitive development,” the authors of the new study said. They went on to explain how improved cognitive outcomes in breastfed infants could potentially be explained by other characteristics of the women, such as “socioeconomics and maternal intelligence.”
 

Important at the population level

For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford (England) set out to investigate how much these confounders influenced the association between breastfeeding duration and cognitive development.

They analyzed data from the U.K. Millennium Cohort Study on 7,855 infants born in 2000 to 2002 and followed until age 14. They highlighted that although the cohort was not specifically designed to address the association between breastfeeding and cognition, it included information on duration of any breastfeeding, duration of exclusive breastfeeding, verbal cognitive scores at ages 5, 7, 11, and 14, spatial cognitive scores at ages 5, 7, and 11, as well as potential confounders, including socioeconomic characteristics and maternal cognition, based on a vocabulary test.

The researchers discovered that longer breastfeeding durations were associated with higher verbal and spatial cognitive scores at all ages up to 14 and 11, respectively.

After taking the differences in socioeconomic position and maternal cognitive ability into account, those children who were breastfed for longer scored higher in cognitive measures up to age 14, compared with children who were not breastfed. They also found that longer breastfeeding durations were associated with mean cognitive scores 0.08-0.26 standard deviations higher than the mean cognitive score of those who were never breastfed. “This difference may seem small for an individual child but could be important at the population level,” the authors commented.
 

Modest effect

In the United Kingdom, women who have more educational qualifications and are more economically advantaged tend to breastfeed for longer, said the authors. In addition, they added, this group tends to “score more highly on cognitive tests.”

These differences could explain why babies who breastfeed for longer do better in cognitive assessments. However, they said that in their study, “we found that even after taking these differences into account, children breastfed for longer scored higher in cognitive measures up to age 14, in comparison to children who were not breastfed.”

The authors explained that the association between breastfeeding duration and cognitive scores “persists after adjusting for socioeconomics and maternal intelligence.” However, they pointed out that “the effect was modest.”

A version of this article first appeared on Medscape UK.

Breastfeeding duration is associated with improved cognitive scores at ages 5-14, even after controlling for maternal socioeconomic position and cognitive ability, said the researchers behind a new study.

Despite previous studies demonstrating an association between breastfeeding and standardized intelligence test scores – with breastfed infants scoring higher on intelligence tests than non-breastfed infants – a causal relationship is still contested.

“There is some debate about whether breastfeeding a baby for a longer period of time improves their cognitive development,” the authors of the new study said. They went on to explain how improved cognitive outcomes in breastfed infants could potentially be explained by other characteristics of the women, such as “socioeconomics and maternal intelligence.”
 

Important at the population level

For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford (England) set out to investigate how much these confounders influenced the association between breastfeeding duration and cognitive development.

They analyzed data from the U.K. Millennium Cohort Study on 7,855 infants born in 2000 to 2002 and followed until age 14. They highlighted that although the cohort was not specifically designed to address the association between breastfeeding and cognition, it included information on duration of any breastfeeding, duration of exclusive breastfeeding, verbal cognitive scores at ages 5, 7, 11, and 14, spatial cognitive scores at ages 5, 7, and 11, as well as potential confounders, including socioeconomic characteristics and maternal cognition, based on a vocabulary test.

The researchers discovered that longer breastfeeding durations were associated with higher verbal and spatial cognitive scores at all ages up to 14 and 11, respectively.

After taking the differences in socioeconomic position and maternal cognitive ability into account, those children who were breastfed for longer scored higher in cognitive measures up to age 14, compared with children who were not breastfed. They also found that longer breastfeeding durations were associated with mean cognitive scores 0.08-0.26 standard deviations higher than the mean cognitive score of those who were never breastfed. “This difference may seem small for an individual child but could be important at the population level,” the authors commented.
 

Modest effect

In the United Kingdom, women who have more educational qualifications and are more economically advantaged tend to breastfeed for longer, said the authors. In addition, they added, this group tends to “score more highly on cognitive tests.”

These differences could explain why babies who breastfeed for longer do better in cognitive assessments. However, they said that in their study, “we found that even after taking these differences into account, children breastfed for longer scored higher in cognitive measures up to age 14, in comparison to children who were not breastfed.”

The authors explained that the association between breastfeeding duration and cognitive scores “persists after adjusting for socioeconomics and maternal intelligence.” However, they pointed out that “the effect was modest.”

A version of this article first appeared on Medscape UK.

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

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

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

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

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Severe airway injuries are a “not infrequent” consequence after children swallow button batteries, which are commonly found in many household electronics, according to a systematic review published online in JAMA Otolaryngology–Head & Neck Surgery.

Most literature has focused on esophageal injury, but “the direct apposition of the esophagus to the trachea and recurrent laryngeal nerves also places these children at risk of airway injury, such as tracheoesophageal fistula (TEF) (a life-threatening complication), vocal cord paresis and paralysis, tracheal stenosis, and tracheomalacia,” the researchers wrote.

Led by Justine Philteos, MD, of the department of otolaryngology–head and neck surgery at the University of Toronto, the researchers found that tracheoesophageal fistula and vocal cord paralyses were the two most common airway injuries and often required tracheostomy.

The review included 195 children pulled from the National Capital Poison Center (NCPC) database – more often young children – who had ingested the batteries. The average age at ingestion was 17.8 months and the average time between ingestion and removal was 5.8 days.

Of the 195 children, 29 (15%) underwent tracheostomy, and 11 of the 29 children (38%) ultimately had decannulation. There were 14 deaths from swallowing the batteries. All 14 patients had a TEF. The cause of death was identified for 12 of the patients: Four died of pneumonia or respiratory failure; three of massive hematemesis; three of sepsis; one of multiorgan failure, and one of anoxic encephalopathy.

Vocal cord injury occurred after a shorter button battery exposure than other airway injuries.

The authors concluded that prioritizing quick button battery removal is essential “to decrease the devastating consequences of these injuries.”

In an invited commentary, Hannah Gibbs, and Kris R. Jatana, MD, of The Ohio State University in Columbus, described what’s being done to prevent and treat these injuries and what’s next.

They noted that ingestion is often unseen so diagnosis is difficult. Therefore, they wrote, a novel coin-battery metal detector could be a radiation-free, quick screening tool. They noted a patent-pending technology has been developed at Ohio State and Nationwide Children’s Hospital.

Honey can help slow injury

Some measures can be taken at home or in the hospital if battery swallowing is discovered, the editorialists noted.

In the home or in transport to the hospital, caregivers can give 10 mL of honey every 10 minutes until arrival if the child is older than 12 months.

At the hospital, 10 mL of either honey or sucralfate may be given every 10 minutes to slow the rate of injury until the battery can be surgically removed.

“The current NCPC guidelines suggest up to six doses may be given in the prehospital setting, with three additional doses administered in the hospital,” they wrote.

“These strategies should be considered earlier than 12 hours from ingestion, when there is no clinical concern for mediastinitis or sepsis. A child with an esophageal button battery should proceed to the operating room immediately regardless of whether he or she has recently eaten,” Ms. Gibbs and Dr. Jatana wrote.
 

App adds convenience to boost physician reporting

Foreign body ingestions are also severely underreported, they noted. They cited a survey of more than 400 physicians who directly manage foreign body ingestions that found only 11% of button battery injuries and 4% of all foreign body ingestion or aspiration events were reported. The great majority (92%) of respondents said they would report the events if that were more convenient.

To that end, the Global Injury Research Collaborative (GIRC) has created and released a free smartphone application, the GIRC App. It is available free on the iOS system (through App Store) and soon will be available on the Android system (through Google Play), they wrote.

Ms. Gibbs and Dr. Jatana urge other measures, including safer battery compartments and battery design, to reduce the likelihood of ingestion.

They pointed out that a bill was introduced in Congress that would require the Consumer Product Safety Commission to mandate a new standard for child-resistant compartments on products containing button batteries. The act, called Reese’s Law, has been referred to the Committee on Energy and Commerce and is under review.

Dr. Jatana reported having a patent pending for a coin or battery metal detector device under development; being a shareholder in Zotarix, Landsdowne Labs, and Tivic Health Systems; serving in a leadership position on the National Button Battery Task Force; and being a board member of the Global Injury Research Collaborative, which is a U.S. Internal Revenue Service–designated, 501(c)(3) nonprofit research organization. No other relevant disclosures were reported.

Severe airway injuries are a “not infrequent” consequence after children swallow button batteries, which are commonly found in many household electronics, according to a systematic review published online in JAMA Otolaryngology–Head & Neck Surgery.

Most literature has focused on esophageal injury, but “the direct apposition of the esophagus to the trachea and recurrent laryngeal nerves also places these children at risk of airway injury, such as tracheoesophageal fistula (TEF) (a life-threatening complication), vocal cord paresis and paralysis, tracheal stenosis, and tracheomalacia,” the researchers wrote.

Led by Justine Philteos, MD, of the department of otolaryngology–head and neck surgery at the University of Toronto, the researchers found that tracheoesophageal fistula and vocal cord paralyses were the two most common airway injuries and often required tracheostomy.

The review included 195 children pulled from the National Capital Poison Center (NCPC) database – more often young children – who had ingested the batteries. The average age at ingestion was 17.8 months and the average time between ingestion and removal was 5.8 days.

Of the 195 children, 29 (15%) underwent tracheostomy, and 11 of the 29 children (38%) ultimately had decannulation. There were 14 deaths from swallowing the batteries. All 14 patients had a TEF. The cause of death was identified for 12 of the patients: Four died of pneumonia or respiratory failure; three of massive hematemesis; three of sepsis; one of multiorgan failure, and one of anoxic encephalopathy.

Vocal cord injury occurred after a shorter button battery exposure than other airway injuries.

The authors concluded that prioritizing quick button battery removal is essential “to decrease the devastating consequences of these injuries.”

In an invited commentary, Hannah Gibbs, and Kris R. Jatana, MD, of The Ohio State University in Columbus, described what’s being done to prevent and treat these injuries and what’s next.

They noted that ingestion is often unseen so diagnosis is difficult. Therefore, they wrote, a novel coin-battery metal detector could be a radiation-free, quick screening tool. They noted a patent-pending technology has been developed at Ohio State and Nationwide Children’s Hospital.

Honey can help slow injury

Some measures can be taken at home or in the hospital if battery swallowing is discovered, the editorialists noted.

In the home or in transport to the hospital, caregivers can give 10 mL of honey every 10 minutes until arrival if the child is older than 12 months.

At the hospital, 10 mL of either honey or sucralfate may be given every 10 minutes to slow the rate of injury until the battery can be surgically removed.

“The current NCPC guidelines suggest up to six doses may be given in the prehospital setting, with three additional doses administered in the hospital,” they wrote.

“These strategies should be considered earlier than 12 hours from ingestion, when there is no clinical concern for mediastinitis or sepsis. A child with an esophageal button battery should proceed to the operating room immediately regardless of whether he or she has recently eaten,” Ms. Gibbs and Dr. Jatana wrote.
 

App adds convenience to boost physician reporting

Foreign body ingestions are also severely underreported, they noted. They cited a survey of more than 400 physicians who directly manage foreign body ingestions that found only 11% of button battery injuries and 4% of all foreign body ingestion or aspiration events were reported. The great majority (92%) of respondents said they would report the events if that were more convenient.

To that end, the Global Injury Research Collaborative (GIRC) has created and released a free smartphone application, the GIRC App. It is available free on the iOS system (through App Store) and soon will be available on the Android system (through Google Play), they wrote.

Ms. Gibbs and Dr. Jatana urge other measures, including safer battery compartments and battery design, to reduce the likelihood of ingestion.

They pointed out that a bill was introduced in Congress that would require the Consumer Product Safety Commission to mandate a new standard for child-resistant compartments on products containing button batteries. The act, called Reese’s Law, has been referred to the Committee on Energy and Commerce and is under review.

Dr. Jatana reported having a patent pending for a coin or battery metal detector device under development; being a shareholder in Zotarix, Landsdowne Labs, and Tivic Health Systems; serving in a leadership position on the National Button Battery Task Force; and being a board member of the Global Injury Research Collaborative, which is a U.S. Internal Revenue Service–designated, 501(c)(3) nonprofit research organization. No other relevant disclosures were reported.

Severe airway injuries are a “not infrequent” consequence after children swallow button batteries, which are commonly found in many household electronics, according to a systematic review published online in JAMA Otolaryngology–Head & Neck Surgery.

Most literature has focused on esophageal injury, but “the direct apposition of the esophagus to the trachea and recurrent laryngeal nerves also places these children at risk of airway injury, such as tracheoesophageal fistula (TEF) (a life-threatening complication), vocal cord paresis and paralysis, tracheal stenosis, and tracheomalacia,” the researchers wrote.

Led by Justine Philteos, MD, of the department of otolaryngology–head and neck surgery at the University of Toronto, the researchers found that tracheoesophageal fistula and vocal cord paralyses were the two most common airway injuries and often required tracheostomy.

The review included 195 children pulled from the National Capital Poison Center (NCPC) database – more often young children – who had ingested the batteries. The average age at ingestion was 17.8 months and the average time between ingestion and removal was 5.8 days.

Of the 195 children, 29 (15%) underwent tracheostomy, and 11 of the 29 children (38%) ultimately had decannulation. There were 14 deaths from swallowing the batteries. All 14 patients had a TEF. The cause of death was identified for 12 of the patients: Four died of pneumonia or respiratory failure; three of massive hematemesis; three of sepsis; one of multiorgan failure, and one of anoxic encephalopathy.

Vocal cord injury occurred after a shorter button battery exposure than other airway injuries.

The authors concluded that prioritizing quick button battery removal is essential “to decrease the devastating consequences of these injuries.”

In an invited commentary, Hannah Gibbs, and Kris R. Jatana, MD, of The Ohio State University in Columbus, described what’s being done to prevent and treat these injuries and what’s next.

They noted that ingestion is often unseen so diagnosis is difficult. Therefore, they wrote, a novel coin-battery metal detector could be a radiation-free, quick screening tool. They noted a patent-pending technology has been developed at Ohio State and Nationwide Children’s Hospital.

Honey can help slow injury

Some measures can be taken at home or in the hospital if battery swallowing is discovered, the editorialists noted.

In the home or in transport to the hospital, caregivers can give 10 mL of honey every 10 minutes until arrival if the child is older than 12 months.

At the hospital, 10 mL of either honey or sucralfate may be given every 10 minutes to slow the rate of injury until the battery can be surgically removed.

“The current NCPC guidelines suggest up to six doses may be given in the prehospital setting, with three additional doses administered in the hospital,” they wrote.

“These strategies should be considered earlier than 12 hours from ingestion, when there is no clinical concern for mediastinitis or sepsis. A child with an esophageal button battery should proceed to the operating room immediately regardless of whether he or she has recently eaten,” Ms. Gibbs and Dr. Jatana wrote.
 

App adds convenience to boost physician reporting

Foreign body ingestions are also severely underreported, they noted. They cited a survey of more than 400 physicians who directly manage foreign body ingestions that found only 11% of button battery injuries and 4% of all foreign body ingestion or aspiration events were reported. The great majority (92%) of respondents said they would report the events if that were more convenient.

To that end, the Global Injury Research Collaborative (GIRC) has created and released a free smartphone application, the GIRC App. It is available free on the iOS system (through App Store) and soon will be available on the Android system (through Google Play), they wrote.

Ms. Gibbs and Dr. Jatana urge other measures, including safer battery compartments and battery design, to reduce the likelihood of ingestion.

They pointed out that a bill was introduced in Congress that would require the Consumer Product Safety Commission to mandate a new standard for child-resistant compartments on products containing button batteries. The act, called Reese’s Law, has been referred to the Committee on Energy and Commerce and is under review.

Dr. Jatana reported having a patent pending for a coin or battery metal detector device under development; being a shareholder in Zotarix, Landsdowne Labs, and Tivic Health Systems; serving in a leadership position on the National Button Battery Task Force; and being a board member of the Global Injury Research Collaborative, which is a U.S. Internal Revenue Service–designated, 501(c)(3) nonprofit research organization. No other relevant disclosures were reported.

Eosinophilic GI diseases (EGIDs) often overlap with other eosinophil-associated diseases (EADs), which leads to greater health care costs, according to an analysis of the U.S. Optum Clinformatics claims database.

EADs have gained increased attention in recent years. They include eosinophilic esophagitis (EoE), eosinophilic asthma, bullous pemphigoid, eosinophilic granulomatosis with polyangiitis, eosinophilic gastritis/gastroenteritis (EG/EGE), and a subset of non–cystic fibrosis bronchiectasis. All involve infiltration of eosinophils, but the exact immune mechanisms behind them seem to vary and are poorly understood, according to Justin Kwiatek, PharmD, who presented the results at the annual Digestive Disease Week^® (DDW).

“We do know that the suitable course of treatment is dependent on the organs impacted. From this study, we also know that EoE mostly exists on its own, with only a small portion also being diagnosed with asthma, while overlap with other EGIDs tends to be higher. This could be because EoE appears to be pathologically different from other EGIDs in the gastrointestinal tract such as eosinophilic gastritis in the stomach or eosinophilic gastroenteritis in the stomach and small bowel. Eosinophils are not normally present in the esophagus but are often found in the stomach or small bowel without inflammation,” said Dr. Kwiatek, who is senior global medical affairs leader, respiratory & immunology, at AstraZeneca.

The study is important, said Dhyanesh Patel, MD, who was asked to comment on the study. “There’s been a lot of interest in eosinophilic gastrointestinal diseases recently because there is lack of a clear definition. We need to define it better because we need to figure out treatment options for the patients,” said Dr. Patel, who is an assistant professor of medicine at Vanderbilt University, Nashville, Tenn.

“It highlights that a lot of the patients that have one eosinophilic disease might have other concomitant atopic diseases. [It may be that] you can use one drug to treat all of them together, so I think it’s important to have a multidisciplinary approach where you work with an allergist and you work with an immunologist and treat their eosinophilic gastritis and their asthma together with one drug. That may help reduce medication burden,” said Dr. Patel.

The researchers analyzed records from 1,326,645 diagnosed patients with at least one EAD and at least 2 years following treatment. There were 13,872 patients with EoE, 38.4% of whom had at least one overlapping EAD. Of 1,365 patients with EG/EGE, 57.9% had at least one overlapping EAD.

EADs were associated with higher Charlson Comorbidity Index scores and high blood eosinophil levels (≥ 300 cells/mcL) among EoE patients, but not among EG/EGE patients. Within the EoE group, female gender was linked to more EAD comorbidities: 35% of patients with only EoE were female; 45% of patients with one comorbidity were female, as were 55% of those with two comorbidities and 57% of those with three or more comorbidities. There was no such trend among patients with EG/EGE.

Total health care costs were lower in the absence of one overlapping EAD among both EoE ($2,061 vs. $3,766 per patient per month) and EG/EGE patients ($2,860 vs. $4,053). Costs went up with more overlap: $8,572 for EoE and three or more other EADs, and $10,397 for EG/EGE and three or more other EADs. These costs were largely driven by outpatient care.

“The data shows that patients with eosinophilic gastritis and eosinophilic gastroenteritis are more likely to have overlapping eosinophilic conditions, such as asthma. When diagnosing a patient with EG or EGE, it’s important to monitor any new symptoms closely and to educate them about the risk factors. This is particularly true for patients with elevated blood eosinophil counts. Accounting for comorbidities and establishing a treatment plan early can help to manage the higher health care spend for patients with overlapping conditions,” said Dr. Kwiatek.

Dr. Kwiatek is an employee and stockholder of AstraZeneca, which funded the study and developed benralizumab, a drug that has been granted orphan drug status for EG/EGE and EoE. Optum Clinformatics is a longitudinal database of deidentified data formed by UnitedHealth Group. Dr. Patel has no relevant financial disclosures.

Eosinophilic GI diseases (EGIDs) often overlap with other eosinophil-associated diseases (EADs), which leads to greater health care costs, according to an analysis of the U.S. Optum Clinformatics claims database.

EADs have gained increased attention in recent years. They include eosinophilic esophagitis (EoE), eosinophilic asthma, bullous pemphigoid, eosinophilic granulomatosis with polyangiitis, eosinophilic gastritis/gastroenteritis (EG/EGE), and a subset of non–cystic fibrosis bronchiectasis. All involve infiltration of eosinophils, but the exact immune mechanisms behind them seem to vary and are poorly understood, according to Justin Kwiatek, PharmD, who presented the results at the annual Digestive Disease Week^® (DDW).

“We do know that the suitable course of treatment is dependent on the organs impacted. From this study, we also know that EoE mostly exists on its own, with only a small portion also being diagnosed with asthma, while overlap with other EGIDs tends to be higher. This could be because EoE appears to be pathologically different from other EGIDs in the gastrointestinal tract such as eosinophilic gastritis in the stomach or eosinophilic gastroenteritis in the stomach and small bowel. Eosinophils are not normally present in the esophagus but are often found in the stomach or small bowel without inflammation,” said Dr. Kwiatek, who is senior global medical affairs leader, respiratory & immunology, at AstraZeneca.

The study is important, said Dhyanesh Patel, MD, who was asked to comment on the study. “There’s been a lot of interest in eosinophilic gastrointestinal diseases recently because there is lack of a clear definition. We need to define it better because we need to figure out treatment options for the patients,” said Dr. Patel, who is an assistant professor of medicine at Vanderbilt University, Nashville, Tenn.

“It highlights that a lot of the patients that have one eosinophilic disease might have other concomitant atopic diseases. [It may be that] you can use one drug to treat all of them together, so I think it’s important to have a multidisciplinary approach where you work with an allergist and you work with an immunologist and treat their eosinophilic gastritis and their asthma together with one drug. That may help reduce medication burden,” said Dr. Patel.

The researchers analyzed records from 1,326,645 diagnosed patients with at least one EAD and at least 2 years following treatment. There were 13,872 patients with EoE, 38.4% of whom had at least one overlapping EAD. Of 1,365 patients with EG/EGE, 57.9% had at least one overlapping EAD.

EADs were associated with higher Charlson Comorbidity Index scores and high blood eosinophil levels (≥ 300 cells/mcL) among EoE patients, but not among EG/EGE patients. Within the EoE group, female gender was linked to more EAD comorbidities: 35% of patients with only EoE were female; 45% of patients with one comorbidity were female, as were 55% of those with two comorbidities and 57% of those with three or more comorbidities. There was no such trend among patients with EG/EGE.

Total health care costs were lower in the absence of one overlapping EAD among both EoE ($2,061 vs. $3,766 per patient per month) and EG/EGE patients ($2,860 vs. $4,053). Costs went up with more overlap: $8,572 for EoE and three or more other EADs, and $10,397 for EG/EGE and three or more other EADs. These costs were largely driven by outpatient care.

“The data shows that patients with eosinophilic gastritis and eosinophilic gastroenteritis are more likely to have overlapping eosinophilic conditions, such as asthma. When diagnosing a patient with EG or EGE, it’s important to monitor any new symptoms closely and to educate them about the risk factors. This is particularly true for patients with elevated blood eosinophil counts. Accounting for comorbidities and establishing a treatment plan early can help to manage the higher health care spend for patients with overlapping conditions,” said Dr. Kwiatek.

Dr. Kwiatek is an employee and stockholder of AstraZeneca, which funded the study and developed benralizumab, a drug that has been granted orphan drug status for EG/EGE and EoE. Optum Clinformatics is a longitudinal database of deidentified data formed by UnitedHealth Group. Dr. Patel has no relevant financial disclosures.

Eosinophilic GI diseases (EGIDs) often overlap with other eosinophil-associated diseases (EADs), which leads to greater health care costs, according to an analysis of the U.S. Optum Clinformatics claims database.

EADs have gained increased attention in recent years. They include eosinophilic esophagitis (EoE), eosinophilic asthma, bullous pemphigoid, eosinophilic granulomatosis with polyangiitis, eosinophilic gastritis/gastroenteritis (EG/EGE), and a subset of non–cystic fibrosis bronchiectasis. All involve infiltration of eosinophils, but the exact immune mechanisms behind them seem to vary and are poorly understood, according to Justin Kwiatek, PharmD, who presented the results at the annual Digestive Disease Week^® (DDW).

“We do know that the suitable course of treatment is dependent on the organs impacted. From this study, we also know that EoE mostly exists on its own, with only a small portion also being diagnosed with asthma, while overlap with other EGIDs tends to be higher. This could be because EoE appears to be pathologically different from other EGIDs in the gastrointestinal tract such as eosinophilic gastritis in the stomach or eosinophilic gastroenteritis in the stomach and small bowel. Eosinophils are not normally present in the esophagus but are often found in the stomach or small bowel without inflammation,” said Dr. Kwiatek, who is senior global medical affairs leader, respiratory & immunology, at AstraZeneca.

The study is important, said Dhyanesh Patel, MD, who was asked to comment on the study. “There’s been a lot of interest in eosinophilic gastrointestinal diseases recently because there is lack of a clear definition. We need to define it better because we need to figure out treatment options for the patients,” said Dr. Patel, who is an assistant professor of medicine at Vanderbilt University, Nashville, Tenn.

“It highlights that a lot of the patients that have one eosinophilic disease might have other concomitant atopic diseases. [It may be that] you can use one drug to treat all of them together, so I think it’s important to have a multidisciplinary approach where you work with an allergist and you work with an immunologist and treat their eosinophilic gastritis and their asthma together with one drug. That may help reduce medication burden,” said Dr. Patel.

The researchers analyzed records from 1,326,645 diagnosed patients with at least one EAD and at least 2 years following treatment. There were 13,872 patients with EoE, 38.4% of whom had at least one overlapping EAD. Of 1,365 patients with EG/EGE, 57.9% had at least one overlapping EAD.

EADs were associated with higher Charlson Comorbidity Index scores and high blood eosinophil levels (≥ 300 cells/mcL) among EoE patients, but not among EG/EGE patients. Within the EoE group, female gender was linked to more EAD comorbidities: 35% of patients with only EoE were female; 45% of patients with one comorbidity were female, as were 55% of those with two comorbidities and 57% of those with three or more comorbidities. There was no such trend among patients with EG/EGE.

Total health care costs were lower in the absence of one overlapping EAD among both EoE ($2,061 vs. $3,766 per patient per month) and EG/EGE patients ($2,860 vs. $4,053). Costs went up with more overlap: $8,572 for EoE and three or more other EADs, and $10,397 for EG/EGE and three or more other EADs. These costs were largely driven by outpatient care.

“The data shows that patients with eosinophilic gastritis and eosinophilic gastroenteritis are more likely to have overlapping eosinophilic conditions, such as asthma. When diagnosing a patient with EG or EGE, it’s important to monitor any new symptoms closely and to educate them about the risk factors. This is particularly true for patients with elevated blood eosinophil counts. Accounting for comorbidities and establishing a treatment plan early can help to manage the higher health care spend for patients with overlapping conditions,” said Dr. Kwiatek.

Dr. Kwiatek is an employee and stockholder of AstraZeneca, which funded the study and developed benralizumab, a drug that has been granted orphan drug status for EG/EGE and EoE. Optum Clinformatics is a longitudinal database of deidentified data formed by UnitedHealth Group. Dr. Patel has no relevant financial disclosures.

Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.

Acute exposure to fine inhalable particles of as little as 2.5 mcm (PM2.5) in diameter can cause a decrease in lung function leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.

The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.

Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.

The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).

A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).

A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.

Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m³) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m³).

What does air pollution have to do with climate change? They both come from the burning of fossil fuels

Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.

The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.

Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.

Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.

Acute exposure to fine inhalable particles of as little as 2.5 mcm (PM2.5) in diameter can cause a decrease in lung function leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.

The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.

Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.

The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).

A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).

A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.

Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m³) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m³).

What does air pollution have to do with climate change? They both come from the burning of fossil fuels

Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.

The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.

Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.

Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.

Acute exposure to fine inhalable particles of as little as 2.5 mcm (PM2.5) in diameter can cause a decrease in lung function leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.

The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.

Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.

The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).

A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).

A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.

Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m³) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m³).

What does air pollution have to do with climate change? They both come from the burning of fossil fuels

Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.

The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.

Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.

Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.