Hypertension

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

Patients with stage 4 chronic kidney disease (CKD) who were in the DAPA-CKD trial had cardiorenal benefits from dapagliflozin that were similar to those of patients in the overall trial, with no added safety signal.

Sara Freeman/MDedge News

DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) was a landmark study of more than 4,000 patients with CKD, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² and albuminuria with/without type 2 diabetes.

The primary results showed that patients who received the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin for a median of 2.4 years were significantly less likely to have worsening kidney disease or die from all causes than were patients who received placebo.

“This prespecified subanalysis of people with an eGFR < 30 mL/min/1.73 m² [stage 4 CKD] in the DAPA-CKD study shows first, that in this very vulnerable population, use of the SGLT2 inhibitor is safe,” said Chantal Mathieu, MD, PhD.

Furthermore, there was no signal whatsoever of more adverse events and even a trend to fewer events, she said in an email to this news organization.

The analysis also showed that “although now in small numbers (around 300 each in the treated group vs. placebo group), there is no suggestion that the protective effect of dapagliflozin on the renal and cardiovascular front would not happen in this group” with advanced CKD. The efficacy findings just missed statistical significance, noted Dr. Mathieu, of Catholic University, Leuven, Belgium, who was not involved in the study.

Although dapagliflozin is now approved for treating patients with CKD who are at risk of kidney disease progression (on the basis of the DAPA-CKD results), guidelines have not yet been updated to reflect this, lead investigator Glenn M. Chertow, MD, MPH, of Stanford (Calif.) University, told this news organization in an email.

“For clinicians,” Dr. Mathieu said, “this is now the absolute reassurance that we do not have to stop an SGLT2 inhibitor in people with eGFR < 30 mL/min for safety reasons and that we should maintain them at these values for renal and cardiovascular protection!

“I absolutely hope labels will change soon to reflect these observations (and indeed movement on that front is happening),” she continued.

“The American Diabetes Association/European Association for the Study of Diabetes consensus on glucose-lowering therapies in type 2 diabetes already advocated keeping these agents until eGFR 30 mL/min (on the basis of evidence in 2019),” Dr. Mathieu added, “but this study will probably push the statements even further.”

“Of note,” she pointed out, “at these low eGFRs, the glucose-lowering potential of the SGLT2 inhibitor is negligible.”
 

Dapagliflozin risks and benefits in advanced CKD

Based on the DAPA-CKD study, published in the New England Journal of Medicine Oct. 8, 2020, the Food and Drug Administration expanded the indication for dapagliflozin (Farxiga, AstraZeneca) in April of 2021.

However, relatively little is known about the safety and efficacy of SGLT2 inhibitors in patients with advanced CKD, who are particularly vulnerable to cardiovascular events and progressive kidney failure, Dr. Chertow and colleagues wrote.

The DAPA-CKD trial randomized 4,304 patients with CKD 1:1 to dapagliflozin 10 mg/day or placebo, including 624 patients (14%) who had eGFR < 30 mL/min per 1.73 m² and albuminuria at baseline.

Patients in the subgroup with advanced CKD had a mean age of 62 years, and 37% were female. About two-thirds had type 2 diabetes and about one-third had cardiovascular disease.

A total of 293 patients received dapagliflozin and 331 patients received placebo.

During a median follow-up of 2.4 years, patients who received dapagliflozin as opposed to placebo had a lower risk of the primary efficacy outcome – a composite of a 50% or greater sustained decline in eGFR, end-stage kidney disease, or death from cardiovascular or renal causes (hazard ratio, 0.73; 95% confidence interval, 0.53-1.02).

In secondary efficacy outcomes, patients who received dapagliflozin as opposed to placebo also had a lower risk of the following:

• A renal composite outcome – a ≥ 50% sustained decline in eGFR, end-stage kidney disease, or death from renal causes (HR, 0.71; 95% CI, 0.49-1.02).
• A cardiovascular composite outcome comprising cardiovascular death or hospitalization for heart failure (HR, 0.83; 95% CI, 0.45-1.53).
• All-cause mortality (HR, 0.68; 95% CI, 0.39 to 1.21).

The eGFR slope declined by 2.15 mL/min per 1.73 m² per year and by 3.38 mL/min per 1.73 m² per year in the dapagliflozin and placebo groups, respectively (P = .005).

“The trial was not powered to detect a statistically significant difference in the primary and key secondary endpoints in modest-sized subgroups,” the researchers noted.

The researchers limited their safety analysis to serious adverse events or symptoms of volume depletion, kidney-related events, major hypoglycemia, bone fractures, amputations, and potential diabetic ketoacidosis.

There was no evidence of increased risk of these adverse events in patients who received dapagliflozin.

The subanalysis of the DAPA-CKD trial was published July 16 in the Journal of the American Society of Nephrology.

The study was funded by AstraZeneca. Dr. Chertow has received fees from AstraZeneca for the DAPA-CKD trial steering committee. The disclosures of the other authors are listed in the article. Dr. Mathieu has served on the advisory panel/speakers bureau for AstraZeneca. Dr. Chertow and Dr. Mathieu also have financial relationships with many other pharmaceutical companies.

Patients with stage 4 chronic kidney disease (CKD) who were in the DAPA-CKD trial had cardiorenal benefits from dapagliflozin that were similar to those of patients in the overall trial, with no added safety signal.

Sara Freeman/MDedge News

DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) was a landmark study of more than 4,000 patients with CKD, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² and albuminuria with/without type 2 diabetes.

The primary results showed that patients who received the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin for a median of 2.4 years were significantly less likely to have worsening kidney disease or die from all causes than were patients who received placebo.

“This prespecified subanalysis of people with an eGFR < 30 mL/min/1.73 m² [stage 4 CKD] in the DAPA-CKD study shows first, that in this very vulnerable population, use of the SGLT2 inhibitor is safe,” said Chantal Mathieu, MD, PhD.

Furthermore, there was no signal whatsoever of more adverse events and even a trend to fewer events, she said in an email to this news organization.

The analysis also showed that “although now in small numbers (around 300 each in the treated group vs. placebo group), there is no suggestion that the protective effect of dapagliflozin on the renal and cardiovascular front would not happen in this group” with advanced CKD. The efficacy findings just missed statistical significance, noted Dr. Mathieu, of Catholic University, Leuven, Belgium, who was not involved in the study.

Although dapagliflozin is now approved for treating patients with CKD who are at risk of kidney disease progression (on the basis of the DAPA-CKD results), guidelines have not yet been updated to reflect this, lead investigator Glenn M. Chertow, MD, MPH, of Stanford (Calif.) University, told this news organization in an email.

“For clinicians,” Dr. Mathieu said, “this is now the absolute reassurance that we do not have to stop an SGLT2 inhibitor in people with eGFR < 30 mL/min for safety reasons and that we should maintain them at these values for renal and cardiovascular protection!

“I absolutely hope labels will change soon to reflect these observations (and indeed movement on that front is happening),” she continued.

“The American Diabetes Association/European Association for the Study of Diabetes consensus on glucose-lowering therapies in type 2 diabetes already advocated keeping these agents until eGFR 30 mL/min (on the basis of evidence in 2019),” Dr. Mathieu added, “but this study will probably push the statements even further.”

“Of note,” she pointed out, “at these low eGFRs, the glucose-lowering potential of the SGLT2 inhibitor is negligible.”
 

Dapagliflozin risks and benefits in advanced CKD

Based on the DAPA-CKD study, published in the New England Journal of Medicine Oct. 8, 2020, the Food and Drug Administration expanded the indication for dapagliflozin (Farxiga, AstraZeneca) in April of 2021.

However, relatively little is known about the safety and efficacy of SGLT2 inhibitors in patients with advanced CKD, who are particularly vulnerable to cardiovascular events and progressive kidney failure, Dr. Chertow and colleagues wrote.

The DAPA-CKD trial randomized 4,304 patients with CKD 1:1 to dapagliflozin 10 mg/day or placebo, including 624 patients (14%) who had eGFR < 30 mL/min per 1.73 m² and albuminuria at baseline.

Patients in the subgroup with advanced CKD had a mean age of 62 years, and 37% were female. About two-thirds had type 2 diabetes and about one-third had cardiovascular disease.

A total of 293 patients received dapagliflozin and 331 patients received placebo.

During a median follow-up of 2.4 years, patients who received dapagliflozin as opposed to placebo had a lower risk of the primary efficacy outcome – a composite of a 50% or greater sustained decline in eGFR, end-stage kidney disease, or death from cardiovascular or renal causes (hazard ratio, 0.73; 95% confidence interval, 0.53-1.02).

In secondary efficacy outcomes, patients who received dapagliflozin as opposed to placebo also had a lower risk of the following:

• A renal composite outcome – a ≥ 50% sustained decline in eGFR, end-stage kidney disease, or death from renal causes (HR, 0.71; 95% CI, 0.49-1.02).
• A cardiovascular composite outcome comprising cardiovascular death or hospitalization for heart failure (HR, 0.83; 95% CI, 0.45-1.53).
• All-cause mortality (HR, 0.68; 95% CI, 0.39 to 1.21).

The eGFR slope declined by 2.15 mL/min per 1.73 m² per year and by 3.38 mL/min per 1.73 m² per year in the dapagliflozin and placebo groups, respectively (P = .005).

“The trial was not powered to detect a statistically significant difference in the primary and key secondary endpoints in modest-sized subgroups,” the researchers noted.

The researchers limited their safety analysis to serious adverse events or symptoms of volume depletion, kidney-related events, major hypoglycemia, bone fractures, amputations, and potential diabetic ketoacidosis.

There was no evidence of increased risk of these adverse events in patients who received dapagliflozin.

The subanalysis of the DAPA-CKD trial was published July 16 in the Journal of the American Society of Nephrology.

The study was funded by AstraZeneca. Dr. Chertow has received fees from AstraZeneca for the DAPA-CKD trial steering committee. The disclosures of the other authors are listed in the article. Dr. Mathieu has served on the advisory panel/speakers bureau for AstraZeneca. Dr. Chertow and Dr. Mathieu also have financial relationships with many other pharmaceutical companies.

Patients with stage 4 chronic kidney disease (CKD) who were in the DAPA-CKD trial had cardiorenal benefits from dapagliflozin that were similar to those of patients in the overall trial, with no added safety signal.

Sara Freeman/MDedge News

DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) was a landmark study of more than 4,000 patients with CKD, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² and albuminuria with/without type 2 diabetes.

The primary results showed that patients who received the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin for a median of 2.4 years were significantly less likely to have worsening kidney disease or die from all causes than were patients who received placebo.

“This prespecified subanalysis of people with an eGFR < 30 mL/min/1.73 m² [stage 4 CKD] in the DAPA-CKD study shows first, that in this very vulnerable population, use of the SGLT2 inhibitor is safe,” said Chantal Mathieu, MD, PhD.

Furthermore, there was no signal whatsoever of more adverse events and even a trend to fewer events, she said in an email to this news organization.

The analysis also showed that “although now in small numbers (around 300 each in the treated group vs. placebo group), there is no suggestion that the protective effect of dapagliflozin on the renal and cardiovascular front would not happen in this group” with advanced CKD. The efficacy findings just missed statistical significance, noted Dr. Mathieu, of Catholic University, Leuven, Belgium, who was not involved in the study.

Although dapagliflozin is now approved for treating patients with CKD who are at risk of kidney disease progression (on the basis of the DAPA-CKD results), guidelines have not yet been updated to reflect this, lead investigator Glenn M. Chertow, MD, MPH, of Stanford (Calif.) University, told this news organization in an email.

“For clinicians,” Dr. Mathieu said, “this is now the absolute reassurance that we do not have to stop an SGLT2 inhibitor in people with eGFR < 30 mL/min for safety reasons and that we should maintain them at these values for renal and cardiovascular protection!

“I absolutely hope labels will change soon to reflect these observations (and indeed movement on that front is happening),” she continued.

“The American Diabetes Association/European Association for the Study of Diabetes consensus on glucose-lowering therapies in type 2 diabetes already advocated keeping these agents until eGFR 30 mL/min (on the basis of evidence in 2019),” Dr. Mathieu added, “but this study will probably push the statements even further.”

“Of note,” she pointed out, “at these low eGFRs, the glucose-lowering potential of the SGLT2 inhibitor is negligible.”
 

Dapagliflozin risks and benefits in advanced CKD

Based on the DAPA-CKD study, published in the New England Journal of Medicine Oct. 8, 2020, the Food and Drug Administration expanded the indication for dapagliflozin (Farxiga, AstraZeneca) in April of 2021.

However, relatively little is known about the safety and efficacy of SGLT2 inhibitors in patients with advanced CKD, who are particularly vulnerable to cardiovascular events and progressive kidney failure, Dr. Chertow and colleagues wrote.

The DAPA-CKD trial randomized 4,304 patients with CKD 1:1 to dapagliflozin 10 mg/day or placebo, including 624 patients (14%) who had eGFR < 30 mL/min per 1.73 m² and albuminuria at baseline.

Patients in the subgroup with advanced CKD had a mean age of 62 years, and 37% were female. About two-thirds had type 2 diabetes and about one-third had cardiovascular disease.

A total of 293 patients received dapagliflozin and 331 patients received placebo.

During a median follow-up of 2.4 years, patients who received dapagliflozin as opposed to placebo had a lower risk of the primary efficacy outcome – a composite of a 50% or greater sustained decline in eGFR, end-stage kidney disease, or death from cardiovascular or renal causes (hazard ratio, 0.73; 95% confidence interval, 0.53-1.02).

In secondary efficacy outcomes, patients who received dapagliflozin as opposed to placebo also had a lower risk of the following:

• A renal composite outcome – a ≥ 50% sustained decline in eGFR, end-stage kidney disease, or death from renal causes (HR, 0.71; 95% CI, 0.49-1.02).
• A cardiovascular composite outcome comprising cardiovascular death or hospitalization for heart failure (HR, 0.83; 95% CI, 0.45-1.53).
• All-cause mortality (HR, 0.68; 95% CI, 0.39 to 1.21).

The eGFR slope declined by 2.15 mL/min per 1.73 m² per year and by 3.38 mL/min per 1.73 m² per year in the dapagliflozin and placebo groups, respectively (P = .005).

“The trial was not powered to detect a statistically significant difference in the primary and key secondary endpoints in modest-sized subgroups,” the researchers noted.

The researchers limited their safety analysis to serious adverse events or symptoms of volume depletion, kidney-related events, major hypoglycemia, bone fractures, amputations, and potential diabetic ketoacidosis.

There was no evidence of increased risk of these adverse events in patients who received dapagliflozin.

The subanalysis of the DAPA-CKD trial was published July 16 in the Journal of the American Society of Nephrology.

The study was funded by AstraZeneca. Dr. Chertow has received fees from AstraZeneca for the DAPA-CKD trial steering committee. The disclosures of the other authors are listed in the article. Dr. Mathieu has served on the advisory panel/speakers bureau for AstraZeneca. Dr. Chertow and Dr. Mathieu also have financial relationships with many other pharmaceutical companies.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

About 87% of Texas physicians reported a “drastic increase over the past 5 years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association, said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says: ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to reengage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said: “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are “an important way” to deliver “safe, high-quality care” to patients, she added.
 

Potential for harm?

Sadeea Abbasi, MD, a practicing physician at Cedars-Sinai in the gastroenterology clinical office in Santa Monica, Calif., can attest that these practices are harmful for her patients.

“Prior authorization requirements have been on the rise across various medical specialties. For GI, we have seen an increase of required approvals for procedures like upper endoscopy, colonoscopy, and wireless capsule endoscopy and in medications prescribed, including biologic infusions for inflammatory bowel disease.”

Dr. Abbasi added: “One of the largest concerns I have with this growing ‘cost-savings’ trend is the impact it has on clinical outcomes. I have seen patients suffer with symptoms while waiting for a decision on a prior authorization for a medication. My patients have endured confusion and chaos when arriving for imaging appointments, only to learn the insurance has not reached a decision on whether the study is approved. When patients learn their procedure has been delayed, they have to reschedule the appointment, take another day off work, coordinate transportation and most importantly, postpone subsequent treatments to alleviate symptoms.”

According to an AMA survey, almost all physicians (94%) said prior authorization delays care and 79% percent have had patients abandon their recommended treatment because of issues related to prior authorization. This delay causes potentially irreversible damage to patients’ digestive system and increases the likelihood of hospitalization. This is a huge issue for America’s seniors: Medicare Advantage (MA) plans, which represent 24.1 million of the 62 million Medicare beneficiaries, the increase in prior authorization requests has been substantial.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA and nearly 300 other stakeholders, including the American Gastroenterological Association, support the Improving Seniors’ Timely Access to Care Act (H.R. 3173). The legislation includes a provision related to “gold carding,” said Robert Mills, an AMA spokesperson.

The bill aims to establish transparency requirements and standards for prior authorization processes related to MA plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Ensuring prior authorization requests are reviewed by qualified medical personnel.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

This legislation was introduced in the U.S. House of Representatives in May by representatives Suzan DelBene (D-Wash.); Mike Kelly (R-Pa.); Ami Bera, MD (D-Calif.); and Larry Bucshon (R-Ind.), after which it was referred to the House Committee on Energy and Commerce and the House Committee on Ways and Means for consideration.

Gaining support for this legislation is a priority for AGA and as such the legislation will be featured as a top policy request at AGA’s upcoming fall Advocacy Day on Sept. 23. The AGA encourages all physicians to contact their lawmakers, urging for support of the bill in the 117th Congress.

In addition to AGA’s advocacy efforts on prior authorization reform, the Regulatory Relief Coalition, a group of national physician specialty organizations, advocates for regulatory burden reduction in Medicare so that physicians can spend more time treating patients. The physician community has banded together to address prior authorization burdens in our field and improve delivery of patient care. Learn more about prior authorization burdens and the various advocacy efforts being pursued.

With additional reporting by staff from this news organization.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

About 87% of Texas physicians reported a “drastic increase over the past 5 years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association, said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says: ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to reengage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said: “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are “an important way” to deliver “safe, high-quality care” to patients, she added.
 

Potential for harm?

Sadeea Abbasi, MD, a practicing physician at Cedars-Sinai in the gastroenterology clinical office in Santa Monica, Calif., can attest that these practices are harmful for her patients.

“Prior authorization requirements have been on the rise across various medical specialties. For GI, we have seen an increase of required approvals for procedures like upper endoscopy, colonoscopy, and wireless capsule endoscopy and in medications prescribed, including biologic infusions for inflammatory bowel disease.”

Dr. Abbasi added: “One of the largest concerns I have with this growing ‘cost-savings’ trend is the impact it has on clinical outcomes. I have seen patients suffer with symptoms while waiting for a decision on a prior authorization for a medication. My patients have endured confusion and chaos when arriving for imaging appointments, only to learn the insurance has not reached a decision on whether the study is approved. When patients learn their procedure has been delayed, they have to reschedule the appointment, take another day off work, coordinate transportation and most importantly, postpone subsequent treatments to alleviate symptoms.”

According to an AMA survey, almost all physicians (94%) said prior authorization delays care and 79% percent have had patients abandon their recommended treatment because of issues related to prior authorization. This delay causes potentially irreversible damage to patients’ digestive system and increases the likelihood of hospitalization. This is a huge issue for America’s seniors: Medicare Advantage (MA) plans, which represent 24.1 million of the 62 million Medicare beneficiaries, the increase in prior authorization requests has been substantial.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA and nearly 300 other stakeholders, including the American Gastroenterological Association, support the Improving Seniors’ Timely Access to Care Act (H.R. 3173). The legislation includes a provision related to “gold carding,” said Robert Mills, an AMA spokesperson.

The bill aims to establish transparency requirements and standards for prior authorization processes related to MA plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Ensuring prior authorization requests are reviewed by qualified medical personnel.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

This legislation was introduced in the U.S. House of Representatives in May by representatives Suzan DelBene (D-Wash.); Mike Kelly (R-Pa.); Ami Bera, MD (D-Calif.); and Larry Bucshon (R-Ind.), after which it was referred to the House Committee on Energy and Commerce and the House Committee on Ways and Means for consideration.

Gaining support for this legislation is a priority for AGA and as such the legislation will be featured as a top policy request at AGA’s upcoming fall Advocacy Day on Sept. 23. The AGA encourages all physicians to contact their lawmakers, urging for support of the bill in the 117th Congress.

In addition to AGA’s advocacy efforts on prior authorization reform, the Regulatory Relief Coalition, a group of national physician specialty organizations, advocates for regulatory burden reduction in Medicare so that physicians can spend more time treating patients. The physician community has banded together to address prior authorization burdens in our field and improve delivery of patient care. Learn more about prior authorization burdens and the various advocacy efforts being pursued.

With additional reporting by staff from this news organization.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

About 87% of Texas physicians reported a “drastic increase over the past 5 years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association, said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says: ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to reengage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said: “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are “an important way” to deliver “safe, high-quality care” to patients, she added.
 

Potential for harm?

Sadeea Abbasi, MD, a practicing physician at Cedars-Sinai in the gastroenterology clinical office in Santa Monica, Calif., can attest that these practices are harmful for her patients.

“Prior authorization requirements have been on the rise across various medical specialties. For GI, we have seen an increase of required approvals for procedures like upper endoscopy, colonoscopy, and wireless capsule endoscopy and in medications prescribed, including biologic infusions for inflammatory bowel disease.”

Dr. Abbasi added: “One of the largest concerns I have with this growing ‘cost-savings’ trend is the impact it has on clinical outcomes. I have seen patients suffer with symptoms while waiting for a decision on a prior authorization for a medication. My patients have endured confusion and chaos when arriving for imaging appointments, only to learn the insurance has not reached a decision on whether the study is approved. When patients learn their procedure has been delayed, they have to reschedule the appointment, take another day off work, coordinate transportation and most importantly, postpone subsequent treatments to alleviate symptoms.”

According to an AMA survey, almost all physicians (94%) said prior authorization delays care and 79% percent have had patients abandon their recommended treatment because of issues related to prior authorization. This delay causes potentially irreversible damage to patients’ digestive system and increases the likelihood of hospitalization. This is a huge issue for America’s seniors: Medicare Advantage (MA) plans, which represent 24.1 million of the 62 million Medicare beneficiaries, the increase in prior authorization requests has been substantial.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA and nearly 300 other stakeholders, including the American Gastroenterological Association, support the Improving Seniors’ Timely Access to Care Act (H.R. 3173). The legislation includes a provision related to “gold carding,” said Robert Mills, an AMA spokesperson.

The bill aims to establish transparency requirements and standards for prior authorization processes related to MA plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Ensuring prior authorization requests are reviewed by qualified medical personnel.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

This legislation was introduced in the U.S. House of Representatives in May by representatives Suzan DelBene (D-Wash.); Mike Kelly (R-Pa.); Ami Bera, MD (D-Calif.); and Larry Bucshon (R-Ind.), after which it was referred to the House Committee on Energy and Commerce and the House Committee on Ways and Means for consideration.

Gaining support for this legislation is a priority for AGA and as such the legislation will be featured as a top policy request at AGA’s upcoming fall Advocacy Day on Sept. 23. The AGA encourages all physicians to contact their lawmakers, urging for support of the bill in the 117th Congress.

In addition to AGA’s advocacy efforts on prior authorization reform, the Regulatory Relief Coalition, a group of national physician specialty organizations, advocates for regulatory burden reduction in Medicare so that physicians can spend more time treating patients. The physician community has banded together to address prior authorization burdens in our field and improve delivery of patient care. Learn more about prior authorization burdens and the various advocacy efforts being pursued.

With additional reporting by staff from this news organization.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Liraglutide and insulin glargine outperformed glimepiride and sitagliptin as single add-on agents to metformin for treating patients with type 2 diabetes in a multicenter U.S. trial that randomized just over 5,000 patients.

The GRADE trial ran for roughly 5 years at 36 U.S. centers and was designed to answer the question of which is the best second-line agent for patients with type 2 diabetes already taking metformin. Results were reported at the virtual American Diabetes Association (ADA) 81st Scientific Sessions. 

The comparison included two oral medications – the sulfonylurea glimepiride and dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin – and two injectable medications – insulin glargine and glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide.

The primary endpoint was change in A1c level and overall glycemic control. Secondary endpoints include changes in weight, as well as cardiovascular, renal, gastrointestinal, and other complications.

For the primary endpoint – keeping A1c levels below 7% – liraglutide and the basal insulin glargine both did this best and were almost equivalent.

During the average 5-year follow-up, the rates of patients progressing to a confirmed A1c of 7% or higher were 67% among patients randomized to insulin glargine, 68% maintained on liraglutide, 72% taking the sulfonylurea glimepiride, and 77% taking sitagliptin, reported John M. Lachin, ScD, a biostatistician at George Washington University, Washington.
 

Too soon for take-aways, or are the data already obsolete?

“The ultimate goal of GRADE is to help clinicians select the therapies that will work best for individual patients, as diabetes care is not a one-size-fits all approach,” noted David M. Nathan, MD, chair of the study and director of the Diabetes Center at Massachusetts General Hospital, in an ADA press release.

Dr. Nathan, as well as several other members of the GRADE trial steering committee who presented results, repeatedly cautioned that the findings were preliminary because they represent 90% of outcomes, with the remaining 10% still to be adjudicated.

“We undertook this study to fill a gap in the guidelines,” said investigator Deborah J. Wexler, MD, clinical director of the Diabetes Center at Massachusetts General Hospital in Boston. “I would like to have all the results in ... before I comment on how the guidelines should change.”

“The metabolic data are solid, but the cardiovascular disease data are preliminary,” warned Dr. Nathan.

But that didn’t stop some from drawing their own conclusions, with Julio Rosenstock, MD, who comoderated the session but was not involved with the study, giving his own opinion.

“A pleasant surprise was the performance of basal insulin,” he said, calling the findings “a vindication” for basal insulin as a treatment for the types of patients with type 2 diabetes that enrolled in the study.

Steven E. Kahn, MB, ChB, another GRADE co-investigator agreed. “Based on the results, guidelines should say that you add insulin early on,” he observed.

A generic basal insulin and a generic sulfonylurea are both reasonable options, after metformin, for patients with limited resources, added Dr. Kahn, an endocrinologist and professor at the University of Washington, Seattle.

Dr. Rosenstock, director of the Dallas Diabetes Research Center, also saw the results as an indictment of agents in the DDP-4 inhibitor class, such as sitagliptin.

The DPP-4 inhibitors generate $9 billion a year, he said, wondering whether it “is justifiable to put them on the same level as other agents?”

Meanwhile the assigned discussant, David R. Matthews, DPhil, a professor of diabetes medicine at the University of Oxford, England – while congratulating the investigators on certain aspects of the study – said it ultimately fell short because it didn’t include an arm with an SGLT2 inhibitor.

“We should kick the authors for missing out on SGLT2 inhibitors,” Dr. Matthews said. “The omission means that the GRADE data are already obsolescent.”

In reply, Dr. Nathan admitted “we feel bad we did not include” an SGLT2 inhibitor, but he vigorously defended the dilemma faced by the trial’s organizers.

Oral SGLT2 inhibitors were not “well-established drugs” for type 2 diabetes when enrollment launched in 2013, and the researchers were wary of including what could turn out to be a problematic agent soon after controversy over the safety of agents in the thiazolidinedione drug class (such as rosiglitazone), he explained.

They also realized that adding a fifth drug to the study would necessitate doubling enrollment size, which would have undercut the funding plans already in place.

Dr. Matthews also derided GRADE as being underpowered to adequately address the impact of the tested agents on major adverse cardiovascular events (MACE) and hospitalizations for heart failure and too U.S.-centric to be generalizable elsewhere.
 

A study with lots of data

The roughly 5,000 patients enrolled in GRADE were an average age of 57 years old, 64% were men, 66% were White, and 20% were Black. They had had type 2 diabetes, on average, for 4.2 years. Mean body mass index at entry was about 34 kg/m², average A1c was 7.5%, and average estimated glomerular filtration rate was 95 mL/min/1.73m². The trial included a 6-12 week run-in period during which background metformin treatment was optimized and led to average A1c levels less than 7%.

Patients were then randomized to one of the four agents as add-on treatment.

Both liraglutide and insulin glargine performed well on many of the numerous metrics in the data-rich trial, largely funded by two branches of the National Institutes of Health, with commercial involvement limited to free supplies of the study drugs.

The secondary metabolic outcome, of disease progressing to a confirmed A1c of 7.5%, was reached by 39% of patients taking insulin glargine, significantly lower than the rate of 46% among patients taking liraglutide, and that rate, in turn, was significantly below the 50% rate among patients taking glimepiride and the 55% rate of those taking sitagliptin.

Mean doses of the second-line agents after 4 years of treatment were 38.3 units/day for glargine, 3.5 mg/day for glimepiride, 1.3 mg/day for subcutaneous liraglutide, and 82.9 mg/day for sitagliptin. 

A trio of cardiovascular outcomes showed one significant benefit of liraglutide over the other three drugs for the endpoint of any cardiovascular event, which included not only major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, or stroke), but also several other event types, including heart failure requiring hospitalization, unstable angina requiring hospitalization, revascularization or any arterial repairs, stent thrombosis, or transient ischemic attack.

For the endpoint of any cardiovascular event, the rate was 5.8% for patients taking liraglutide, significantly less than the rate of 7.6% of those taking insulin glargine, 8.0% for glimepiride, and 8.6% for sitagliptin, reported John B. Buse, MD, PhD, professor, chief of endocrinology, and director of the Diabetes Center at the University of North Carolina at Chapel Hill.

For each of the other two main cardiovascular endpoints – MACE and hospitalization for heart failure – liraglutide had a numeric advantage over the other three drugs but failed to reach significance. 

Patients taking liraglutide also had a smaller but not significantly different point estimate for all-cause death, at 2.1%, compared with 3.1%-3.4% in the other three groups.

And, Dr. Nathan emphasized, the cardiovascular disease data are still considered preliminary.

Liraglutide scored a pair of additional outcome victories. Its use resulted in a significantly lower rate of patients who progressed during follow-up to either needing antihypertensive medications or having their blood pressure rise above 140/90 mm Hg compared with the other three drugs. (At baseline, average blood pressure for all patients was 128/77 mm Hg.)

And after 4 years, patients taking liraglutide lost an average of about 4 kg (8.8 lb) from their baseline weight (which averaged about 100 kg [220 lb]), roughly the same as patients taking sitagliptin but significantly better than with glimepiride or insulin glargine. Patients taking glargine gained a small amount of weight on average during their first couple of years of treatment, roughly 1 kg, but returned to around their baseline weight by the end of 4 years.
 

Four drugs performed equally well for some outcomes

Finally, the four drugs had similar results for some outcomes. This included their effects on renal function, distal sensory polyneuropathy, and low-density lipoprotein (LDL) cholesterol.

The four agents also had roughly similar safety profiles, with rates of serious adverse events all falling within the tight range of 33%-37%.

But the rate of severe hypoglycemic episodes that required assistance to treat showed significant separation, ranging from 2.3% for glimepiride, 1.4% for glargine, 0.9% for liraglutide, and 0.7% for sitagliptin. Gastrointestinal symptoms occurred in about 50% of patients in three of the treatment groups but were significantly higher in those taking liraglutide, affecting 60%.

GRADE received no commercial funding. Dr. Wexler has reported serving on data monitoring committees for Novo Nordisk. Dr. Buse has reported being a consultant for and holding stock in numerous companies. Dr. Rosenstock has reported being an advisor or consultant to Applied Therapeutics, Boehringer Ingelheim, Hanmi Pharmaceutical, Intarcia Therapeutics, Lilly, Novo Nordisk, Oramed, and Sanofi and has received research support from numerous companies. Dr. Kahn has reported being an advisor to or speaker on behalf of Bayer, Boehringer Ingelheim, Casma Therapeutics, Intarcia Therapeutics, Lilly, Merck, Novo Nordisk, Pfizer, and Third Rock Ventures. Dr. Matthews has reported receiving lecture and advisor fees from Merck, Novartis, Novo Nordisk, Sanofi Aventis, and Servier. Dr. Lachin and Dr. Nathan have reported no relevant financial relationships.

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

Liraglutide and insulin glargine outperformed glimepiride and sitagliptin as single add-on agents to metformin for treating patients with type 2 diabetes in a multicenter U.S. trial that randomized just over 5,000 patients.

The GRADE trial ran for roughly 5 years at 36 U.S. centers and was designed to answer the question of which is the best second-line agent for patients with type 2 diabetes already taking metformin. Results were reported at the virtual American Diabetes Association (ADA) 81st Scientific Sessions. 

The comparison included two oral medications – the sulfonylurea glimepiride and dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin – and two injectable medications – insulin glargine and glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide.

The primary endpoint was change in A1c level and overall glycemic control. Secondary endpoints include changes in weight, as well as cardiovascular, renal, gastrointestinal, and other complications.

For the primary endpoint – keeping A1c levels below 7% – liraglutide and the basal insulin glargine both did this best and were almost equivalent.

During the average 5-year follow-up, the rates of patients progressing to a confirmed A1c of 7% or higher were 67% among patients randomized to insulin glargine, 68% maintained on liraglutide, 72% taking the sulfonylurea glimepiride, and 77% taking sitagliptin, reported John M. Lachin, ScD, a biostatistician at George Washington University, Washington.
 

Too soon for take-aways, or are the data already obsolete?

“The ultimate goal of GRADE is to help clinicians select the therapies that will work best for individual patients, as diabetes care is not a one-size-fits all approach,” noted David M. Nathan, MD, chair of the study and director of the Diabetes Center at Massachusetts General Hospital, in an ADA press release.

Dr. Nathan, as well as several other members of the GRADE trial steering committee who presented results, repeatedly cautioned that the findings were preliminary because they represent 90% of outcomes, with the remaining 10% still to be adjudicated.

“We undertook this study to fill a gap in the guidelines,” said investigator Deborah J. Wexler, MD, clinical director of the Diabetes Center at Massachusetts General Hospital in Boston. “I would like to have all the results in ... before I comment on how the guidelines should change.”

“The metabolic data are solid, but the cardiovascular disease data are preliminary,” warned Dr. Nathan.

But that didn’t stop some from drawing their own conclusions, with Julio Rosenstock, MD, who comoderated the session but was not involved with the study, giving his own opinion.

“A pleasant surprise was the performance of basal insulin,” he said, calling the findings “a vindication” for basal insulin as a treatment for the types of patients with type 2 diabetes that enrolled in the study.

Steven E. Kahn, MB, ChB, another GRADE co-investigator agreed. “Based on the results, guidelines should say that you add insulin early on,” he observed.

A generic basal insulin and a generic sulfonylurea are both reasonable options, after metformin, for patients with limited resources, added Dr. Kahn, an endocrinologist and professor at the University of Washington, Seattle.

Dr. Rosenstock, director of the Dallas Diabetes Research Center, also saw the results as an indictment of agents in the DDP-4 inhibitor class, such as sitagliptin.

The DPP-4 inhibitors generate $9 billion a year, he said, wondering whether it “is justifiable to put them on the same level as other agents?”

Meanwhile the assigned discussant, David R. Matthews, DPhil, a professor of diabetes medicine at the University of Oxford, England – while congratulating the investigators on certain aspects of the study – said it ultimately fell short because it didn’t include an arm with an SGLT2 inhibitor.

“We should kick the authors for missing out on SGLT2 inhibitors,” Dr. Matthews said. “The omission means that the GRADE data are already obsolescent.”

In reply, Dr. Nathan admitted “we feel bad we did not include” an SGLT2 inhibitor, but he vigorously defended the dilemma faced by the trial’s organizers.

Oral SGLT2 inhibitors were not “well-established drugs” for type 2 diabetes when enrollment launched in 2013, and the researchers were wary of including what could turn out to be a problematic agent soon after controversy over the safety of agents in the thiazolidinedione drug class (such as rosiglitazone), he explained.

They also realized that adding a fifth drug to the study would necessitate doubling enrollment size, which would have undercut the funding plans already in place.

Dr. Matthews also derided GRADE as being underpowered to adequately address the impact of the tested agents on major adverse cardiovascular events (MACE) and hospitalizations for heart failure and too U.S.-centric to be generalizable elsewhere.
 

A study with lots of data

The roughly 5,000 patients enrolled in GRADE were an average age of 57 years old, 64% were men, 66% were White, and 20% were Black. They had had type 2 diabetes, on average, for 4.2 years. Mean body mass index at entry was about 34 kg/m², average A1c was 7.5%, and average estimated glomerular filtration rate was 95 mL/min/1.73m². The trial included a 6-12 week run-in period during which background metformin treatment was optimized and led to average A1c levels less than 7%.

Patients were then randomized to one of the four agents as add-on treatment.

Both liraglutide and insulin glargine performed well on many of the numerous metrics in the data-rich trial, largely funded by two branches of the National Institutes of Health, with commercial involvement limited to free supplies of the study drugs.

The secondary metabolic outcome, of disease progressing to a confirmed A1c of 7.5%, was reached by 39% of patients taking insulin glargine, significantly lower than the rate of 46% among patients taking liraglutide, and that rate, in turn, was significantly below the 50% rate among patients taking glimepiride and the 55% rate of those taking sitagliptin.

Mean doses of the second-line agents after 4 years of treatment were 38.3 units/day for glargine, 3.5 mg/day for glimepiride, 1.3 mg/day for subcutaneous liraglutide, and 82.9 mg/day for sitagliptin. 

A trio of cardiovascular outcomes showed one significant benefit of liraglutide over the other three drugs for the endpoint of any cardiovascular event, which included not only major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, or stroke), but also several other event types, including heart failure requiring hospitalization, unstable angina requiring hospitalization, revascularization or any arterial repairs, stent thrombosis, or transient ischemic attack.

For the endpoint of any cardiovascular event, the rate was 5.8% for patients taking liraglutide, significantly less than the rate of 7.6% of those taking insulin glargine, 8.0% for glimepiride, and 8.6% for sitagliptin, reported John B. Buse, MD, PhD, professor, chief of endocrinology, and director of the Diabetes Center at the University of North Carolina at Chapel Hill.

For each of the other two main cardiovascular endpoints – MACE and hospitalization for heart failure – liraglutide had a numeric advantage over the other three drugs but failed to reach significance. 

Patients taking liraglutide also had a smaller but not significantly different point estimate for all-cause death, at 2.1%, compared with 3.1%-3.4% in the other three groups.

And, Dr. Nathan emphasized, the cardiovascular disease data are still considered preliminary.

Liraglutide scored a pair of additional outcome victories. Its use resulted in a significantly lower rate of patients who progressed during follow-up to either needing antihypertensive medications or having their blood pressure rise above 140/90 mm Hg compared with the other three drugs. (At baseline, average blood pressure for all patients was 128/77 mm Hg.)

And after 4 years, patients taking liraglutide lost an average of about 4 kg (8.8 lb) from their baseline weight (which averaged about 100 kg [220 lb]), roughly the same as patients taking sitagliptin but significantly better than with glimepiride or insulin glargine. Patients taking glargine gained a small amount of weight on average during their first couple of years of treatment, roughly 1 kg, but returned to around their baseline weight by the end of 4 years.
 

Four drugs performed equally well for some outcomes

Finally, the four drugs had similar results for some outcomes. This included their effects on renal function, distal sensory polyneuropathy, and low-density lipoprotein (LDL) cholesterol.

The four agents also had roughly similar safety profiles, with rates of serious adverse events all falling within the tight range of 33%-37%.

But the rate of severe hypoglycemic episodes that required assistance to treat showed significant separation, ranging from 2.3% for glimepiride, 1.4% for glargine, 0.9% for liraglutide, and 0.7% for sitagliptin. Gastrointestinal symptoms occurred in about 50% of patients in three of the treatment groups but were significantly higher in those taking liraglutide, affecting 60%.

GRADE received no commercial funding. Dr. Wexler has reported serving on data monitoring committees for Novo Nordisk. Dr. Buse has reported being a consultant for and holding stock in numerous companies. Dr. Rosenstock has reported being an advisor or consultant to Applied Therapeutics, Boehringer Ingelheim, Hanmi Pharmaceutical, Intarcia Therapeutics, Lilly, Novo Nordisk, Oramed, and Sanofi and has received research support from numerous companies. Dr. Kahn has reported being an advisor to or speaker on behalf of Bayer, Boehringer Ingelheim, Casma Therapeutics, Intarcia Therapeutics, Lilly, Merck, Novo Nordisk, Pfizer, and Third Rock Ventures. Dr. Matthews has reported receiving lecture and advisor fees from Merck, Novartis, Novo Nordisk, Sanofi Aventis, and Servier. Dr. Lachin and Dr. Nathan have reported no relevant financial relationships.

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

Liraglutide and insulin glargine outperformed glimepiride and sitagliptin as single add-on agents to metformin for treating patients with type 2 diabetes in a multicenter U.S. trial that randomized just over 5,000 patients.

The GRADE trial ran for roughly 5 years at 36 U.S. centers and was designed to answer the question of which is the best second-line agent for patients with type 2 diabetes already taking metformin. Results were reported at the virtual American Diabetes Association (ADA) 81st Scientific Sessions. 

The comparison included two oral medications – the sulfonylurea glimepiride and dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin – and two injectable medications – insulin glargine and glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide.

The primary endpoint was change in A1c level and overall glycemic control. Secondary endpoints include changes in weight, as well as cardiovascular, renal, gastrointestinal, and other complications.

For the primary endpoint – keeping A1c levels below 7% – liraglutide and the basal insulin glargine both did this best and were almost equivalent.

During the average 5-year follow-up, the rates of patients progressing to a confirmed A1c of 7% or higher were 67% among patients randomized to insulin glargine, 68% maintained on liraglutide, 72% taking the sulfonylurea glimepiride, and 77% taking sitagliptin, reported John M. Lachin, ScD, a biostatistician at George Washington University, Washington.
 

Too soon for take-aways, or are the data already obsolete?

“The ultimate goal of GRADE is to help clinicians select the therapies that will work best for individual patients, as diabetes care is not a one-size-fits all approach,” noted David M. Nathan, MD, chair of the study and director of the Diabetes Center at Massachusetts General Hospital, in an ADA press release.

Dr. Nathan, as well as several other members of the GRADE trial steering committee who presented results, repeatedly cautioned that the findings were preliminary because they represent 90% of outcomes, with the remaining 10% still to be adjudicated.

“We undertook this study to fill a gap in the guidelines,” said investigator Deborah J. Wexler, MD, clinical director of the Diabetes Center at Massachusetts General Hospital in Boston. “I would like to have all the results in ... before I comment on how the guidelines should change.”

“The metabolic data are solid, but the cardiovascular disease data are preliminary,” warned Dr. Nathan.

But that didn’t stop some from drawing their own conclusions, with Julio Rosenstock, MD, who comoderated the session but was not involved with the study, giving his own opinion.

“A pleasant surprise was the performance of basal insulin,” he said, calling the findings “a vindication” for basal insulin as a treatment for the types of patients with type 2 diabetes that enrolled in the study.

Steven E. Kahn, MB, ChB, another GRADE co-investigator agreed. “Based on the results, guidelines should say that you add insulin early on,” he observed.

A generic basal insulin and a generic sulfonylurea are both reasonable options, after metformin, for patients with limited resources, added Dr. Kahn, an endocrinologist and professor at the University of Washington, Seattle.

Dr. Rosenstock, director of the Dallas Diabetes Research Center, also saw the results as an indictment of agents in the DDP-4 inhibitor class, such as sitagliptin.

The DPP-4 inhibitors generate $9 billion a year, he said, wondering whether it “is justifiable to put them on the same level as other agents?”

Meanwhile the assigned discussant, David R. Matthews, DPhil, a professor of diabetes medicine at the University of Oxford, England – while congratulating the investigators on certain aspects of the study – said it ultimately fell short because it didn’t include an arm with an SGLT2 inhibitor.

“We should kick the authors for missing out on SGLT2 inhibitors,” Dr. Matthews said. “The omission means that the GRADE data are already obsolescent.”

In reply, Dr. Nathan admitted “we feel bad we did not include” an SGLT2 inhibitor, but he vigorously defended the dilemma faced by the trial’s organizers.

Oral SGLT2 inhibitors were not “well-established drugs” for type 2 diabetes when enrollment launched in 2013, and the researchers were wary of including what could turn out to be a problematic agent soon after controversy over the safety of agents in the thiazolidinedione drug class (such as rosiglitazone), he explained.

They also realized that adding a fifth drug to the study would necessitate doubling enrollment size, which would have undercut the funding plans already in place.

Dr. Matthews also derided GRADE as being underpowered to adequately address the impact of the tested agents on major adverse cardiovascular events (MACE) and hospitalizations for heart failure and too U.S.-centric to be generalizable elsewhere.
 

A study with lots of data

The roughly 5,000 patients enrolled in GRADE were an average age of 57 years old, 64% were men, 66% were White, and 20% were Black. They had had type 2 diabetes, on average, for 4.2 years. Mean body mass index at entry was about 34 kg/m², average A1c was 7.5%, and average estimated glomerular filtration rate was 95 mL/min/1.73m². The trial included a 6-12 week run-in period during which background metformin treatment was optimized and led to average A1c levels less than 7%.

Patients were then randomized to one of the four agents as add-on treatment.

Both liraglutide and insulin glargine performed well on many of the numerous metrics in the data-rich trial, largely funded by two branches of the National Institutes of Health, with commercial involvement limited to free supplies of the study drugs.

The secondary metabolic outcome, of disease progressing to a confirmed A1c of 7.5%, was reached by 39% of patients taking insulin glargine, significantly lower than the rate of 46% among patients taking liraglutide, and that rate, in turn, was significantly below the 50% rate among patients taking glimepiride and the 55% rate of those taking sitagliptin.

Mean doses of the second-line agents after 4 years of treatment were 38.3 units/day for glargine, 3.5 mg/day for glimepiride, 1.3 mg/day for subcutaneous liraglutide, and 82.9 mg/day for sitagliptin. 

A trio of cardiovascular outcomes showed one significant benefit of liraglutide over the other three drugs for the endpoint of any cardiovascular event, which included not only major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, or stroke), but also several other event types, including heart failure requiring hospitalization, unstable angina requiring hospitalization, revascularization or any arterial repairs, stent thrombosis, or transient ischemic attack.

For the endpoint of any cardiovascular event, the rate was 5.8% for patients taking liraglutide, significantly less than the rate of 7.6% of those taking insulin glargine, 8.0% for glimepiride, and 8.6% for sitagliptin, reported John B. Buse, MD, PhD, professor, chief of endocrinology, and director of the Diabetes Center at the University of North Carolina at Chapel Hill.

For each of the other two main cardiovascular endpoints – MACE and hospitalization for heart failure – liraglutide had a numeric advantage over the other three drugs but failed to reach significance. 

Patients taking liraglutide also had a smaller but not significantly different point estimate for all-cause death, at 2.1%, compared with 3.1%-3.4% in the other three groups.

And, Dr. Nathan emphasized, the cardiovascular disease data are still considered preliminary.

Liraglutide scored a pair of additional outcome victories. Its use resulted in a significantly lower rate of patients who progressed during follow-up to either needing antihypertensive medications or having their blood pressure rise above 140/90 mm Hg compared with the other three drugs. (At baseline, average blood pressure for all patients was 128/77 mm Hg.)

And after 4 years, patients taking liraglutide lost an average of about 4 kg (8.8 lb) from their baseline weight (which averaged about 100 kg [220 lb]), roughly the same as patients taking sitagliptin but significantly better than with glimepiride or insulin glargine. Patients taking glargine gained a small amount of weight on average during their first couple of years of treatment, roughly 1 kg, but returned to around their baseline weight by the end of 4 years.
 

Four drugs performed equally well for some outcomes

Finally, the four drugs had similar results for some outcomes. This included their effects on renal function, distal sensory polyneuropathy, and low-density lipoprotein (LDL) cholesterol.

The four agents also had roughly similar safety profiles, with rates of serious adverse events all falling within the tight range of 33%-37%.

But the rate of severe hypoglycemic episodes that required assistance to treat showed significant separation, ranging from 2.3% for glimepiride, 1.4% for glargine, 0.9% for liraglutide, and 0.7% for sitagliptin. Gastrointestinal symptoms occurred in about 50% of patients in three of the treatment groups but were significantly higher in those taking liraglutide, affecting 60%.

GRADE received no commercial funding. Dr. Wexler has reported serving on data monitoring committees for Novo Nordisk. Dr. Buse has reported being a consultant for and holding stock in numerous companies. Dr. Rosenstock has reported being an advisor or consultant to Applied Therapeutics, Boehringer Ingelheim, Hanmi Pharmaceutical, Intarcia Therapeutics, Lilly, Novo Nordisk, Oramed, and Sanofi and has received research support from numerous companies. Dr. Kahn has reported being an advisor to or speaker on behalf of Bayer, Boehringer Ingelheim, Casma Therapeutics, Intarcia Therapeutics, Lilly, Merck, Novo Nordisk, Pfizer, and Third Rock Ventures. Dr. Matthews has reported receiving lecture and advisor fees from Merck, Novartis, Novo Nordisk, Sanofi Aventis, and Servier. Dr. Lachin and Dr. Nathan have reported no relevant financial relationships.

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

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

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

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

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

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

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

Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.

In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.

Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.

The article was published online June 14, 2021, in JAMA Network Open.

Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.

Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”

The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.

The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.

Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.

Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)

The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.

“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
 

Findings no surprise

Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.

“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.

Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.

Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.

“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.

Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”

The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.

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

Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.

In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.

Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.

The article was published online June 14, 2021, in JAMA Network Open.

Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.

Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”

The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.

The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.

Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.

Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)

The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.

“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
 

Findings no surprise

Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.

“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.

Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.

Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.

“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.

Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”

The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.

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

Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.

In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.

Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.

The article was published online June 14, 2021, in JAMA Network Open.

Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.

Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”

The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.

The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.

Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.

Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)

The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.

“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
 

Findings no surprise

Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.

“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.

Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.

Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.

“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.

Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”

The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.

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

Antihypertensive medications that cross the blood-brain barrier (BBB) may be linked with less memory decline, compared with other drugs for high blood pressure, suggest the findings of a meta-analysis.

Over a 3-year period, cognitively normal older adults taking BBB-crossing antihypertensives demonstrated superior verbal memory, compared with similar individuals receiving non–BBB-crossing antihypertensives, reported lead author Jean K. Ho, PhD, of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, and colleagues.

According to the investigators, the findings add color to a known link between hypertension and neurologic degeneration, and may aid the search for new therapeutic targets.

“Hypertension is a well-established risk factor for cognitive decline and dementia, possibly through its effects on both cerebrovascular disease and Alzheimer’s disease,” Dr. Ho and colleagues wrote in Hypertension. “Studies of antihypertensive treatments have reported possible salutary effects on cognition and cerebrovascular disease, as well as Alzheimer’s disease neuropathology.”

In a previous study, individuals younger than 75 years exposed to antihypertensives had an 8% decreased risk of dementia per year of use, while another trial showed that intensive blood pressure–lowering therapy reduced mild cognitive impairment by 19%.

“Despite these encouraging findings ... larger meta-analytic studies have been hampered by the fact that pharmacokinetic properties are typically not considered in existing studies or routine clinical practice,” wrote Dr. Ho and colleagues. “The present study sought to fill this gap [in that it was] a large and longitudinal meta-analytic study of existing data recoded to assess the effects of BBB-crossing potential in renin-angiotensin system [RAS] treatments among hypertensive adults.”
 

Methods and results

The meta-analysis included randomized clinical trials, prospective cohort studies, and retrospective observational studies. The researchers assessed data on 12,849 individuals from 14 cohorts that received either BBB-crossing or non–BBB-crossing antihypertensives.

The BBB-crossing properties of RAS treatments were identified by a literature review. Of ACE inhibitors, captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as BBB crossing, and benazepril, enalapril, moexipril, and quinapril were classified as non–BBB-crossing. Of ARBs, telmisartan and candesartan were considered BBB-crossing, and olmesartan, eprosartan, irbesartan, and losartan were tagged as non–BBB-crossing.

Cognition was assessed via the following seven domains: executive function, attention, verbal memory learning, language, mental status, recall, and processing speed.

Compared with individuals taking non–BBB-crossing antihypertensives, those taking BBB-crossing agents had significantly superior verbal memory (recall), with a maximum effect size of 0.07 (P = .03).

According to the investigators, this finding was particularly noteworthy, as the BBB-crossing group had relatively higher vascular risk burden and lower mean education level.

“These differences make it all the more remarkable that the BBB-crossing group displayed better memory ability over time despite these cognitive disadvantages,” the investigators wrote.

Still, not all the findings favored BBB-crossing agents. Individuals in the BBB-crossing group had relatively inferior attention ability, with a minimum effect size of –0.17 (P = .02).

The other cognitive measures were not significantly different between groups.
 

Clinicians may consider findings after accounting for other factors

Principal investigator Daniel A. Nation, PhD, associate professor of psychological science and a faculty member of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, suggested that the small difference in verbal memory between groups could be clinically significant over a longer period of time.

“Although the overall effect size was pretty small, if you look at how long it would take for someone [with dementia] to progress over many years of decline, it would actually end up being a pretty big effect,” Dr. Nation said in an interview. “Small effect sizes could actually end up preventing a lot of cases of dementia,” he added.

The conflicting results in the BBB-crossing group – better verbal memory but worse attention ability – were “surprising,” he noted.

“I sort of didn’t believe it at first,” Dr. Nation said, “because the memory finding is sort of replication – we’d observed the same exact effect on memory in a smaller sample in another study. ... The attention [finding], going another way, was a new thing.”

Dr. Nation suggested that the intergroup differences in attention ability may stem from idiosyncrasies of the tests used to measure that domain, which can be impacted by cardiovascular or brain vascular disease. Or it could be caused by something else entirely, he said, noting that further investigation is needed.

He added that the improvements in verbal memory within the BBB-crossing group could be caused by direct effects on the brain. He pointed out that certain ACE polymorphisms have been linked with Alzheimer’s disease risk, and those same polymorphisms, in animal models, lead to neurodegeneration, with reversal possible through administration of ACE inhibitors.

“It could be that what we’re observing has nothing really to do with blood pressure,” Dr. Nation explained. “This could be a neuronal effect on learning memory systems.”

He went on to suggest that clinicians may consider these findings when selecting antihypertensive agents for their patients, with the caveat that all other prescribing factors have already been taking to account.

“In the event that you’re going to give an ACE inhibitor or an angiotensin receptor blocker anyway, and it ends up being a somewhat arbitrary decision in terms of which specific drug you’re going to give, then perhaps this is a piece of information you would take into account – that one gets in the brain and one doesn’t – in somebody at risk for cognitive decline,” Dr. Nation said.
 

Exact mechanisms of action unknown

Hélène Girouard, PhD, assistant professor of pharmacology and physiology at the University of Montreal, said in an interview that the findings are “of considerable importance, knowing that brain alterations could begin as much as 30 years before manifestation of dementia.”

Since 2003, Dr. Girouard has been studying the cognitive effects of antihypertensive medications. She noted that previous studies involving rodents “have shown beneficial effects [of BBB-crossing antihypertensive drugs] on cognition independent of their effects on blood pressure.”

The drugs’ exact mechanisms of action, however, remain elusive, according to Dr. Girouard, who offered several possible explanations, including amelioration of BBB disruption, brain inflammation, cerebral blood flow dysregulation, cholinergic dysfunction, and neurologic deficits. “Whether these mechanisms may explain Ho and colleagues’ observations remains to be established,” she added.

Andrea L. Schneider, MD, PhD, assistant professor of neurology at the University of Pennsylvania, Philadelphia, applauded the study, but ultimately suggested that more research is needed to impact clinical decision-making.

“The results of this important and well-done study suggest that further investigation into targeted mechanism-based approaches to selecting hypertension treatment agents, with a specific focus on cognitive outcomes, is warranted,” Dr. Schneider said in an interview. “Before changing clinical practice, further work is necessary to disentangle contributions of medication mechanism, comorbid vascular risk factors, and achieved blood pressure reduction, among others.”

The investigators disclosed support from the National Institutes of Health, the Alzheimer’s Association, the Waksman Foundation of Japan, and others. The interviewees reported no relevant conflicts of interest.

Antihypertensive medications that cross the blood-brain barrier (BBB) may be linked with less memory decline, compared with other drugs for high blood pressure, suggest the findings of a meta-analysis.

Over a 3-year period, cognitively normal older adults taking BBB-crossing antihypertensives demonstrated superior verbal memory, compared with similar individuals receiving non–BBB-crossing antihypertensives, reported lead author Jean K. Ho, PhD, of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, and colleagues.

According to the investigators, the findings add color to a known link between hypertension and neurologic degeneration, and may aid the search for new therapeutic targets.

“Hypertension is a well-established risk factor for cognitive decline and dementia, possibly through its effects on both cerebrovascular disease and Alzheimer’s disease,” Dr. Ho and colleagues wrote in Hypertension. “Studies of antihypertensive treatments have reported possible salutary effects on cognition and cerebrovascular disease, as well as Alzheimer’s disease neuropathology.”

In a previous study, individuals younger than 75 years exposed to antihypertensives had an 8% decreased risk of dementia per year of use, while another trial showed that intensive blood pressure–lowering therapy reduced mild cognitive impairment by 19%.

“Despite these encouraging findings ... larger meta-analytic studies have been hampered by the fact that pharmacokinetic properties are typically not considered in existing studies or routine clinical practice,” wrote Dr. Ho and colleagues. “The present study sought to fill this gap [in that it was] a large and longitudinal meta-analytic study of existing data recoded to assess the effects of BBB-crossing potential in renin-angiotensin system [RAS] treatments among hypertensive adults.”
 

Methods and results

The meta-analysis included randomized clinical trials, prospective cohort studies, and retrospective observational studies. The researchers assessed data on 12,849 individuals from 14 cohorts that received either BBB-crossing or non–BBB-crossing antihypertensives.

The BBB-crossing properties of RAS treatments were identified by a literature review. Of ACE inhibitors, captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as BBB crossing, and benazepril, enalapril, moexipril, and quinapril were classified as non–BBB-crossing. Of ARBs, telmisartan and candesartan were considered BBB-crossing, and olmesartan, eprosartan, irbesartan, and losartan were tagged as non–BBB-crossing.

Cognition was assessed via the following seven domains: executive function, attention, verbal memory learning, language, mental status, recall, and processing speed.

Compared with individuals taking non–BBB-crossing antihypertensives, those taking BBB-crossing agents had significantly superior verbal memory (recall), with a maximum effect size of 0.07 (P = .03).

According to the investigators, this finding was particularly noteworthy, as the BBB-crossing group had relatively higher vascular risk burden and lower mean education level.

“These differences make it all the more remarkable that the BBB-crossing group displayed better memory ability over time despite these cognitive disadvantages,” the investigators wrote.

Still, not all the findings favored BBB-crossing agents. Individuals in the BBB-crossing group had relatively inferior attention ability, with a minimum effect size of –0.17 (P = .02).

The other cognitive measures were not significantly different between groups.
 

Clinicians may consider findings after accounting for other factors

Principal investigator Daniel A. Nation, PhD, associate professor of psychological science and a faculty member of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, suggested that the small difference in verbal memory between groups could be clinically significant over a longer period of time.

“Although the overall effect size was pretty small, if you look at how long it would take for someone [with dementia] to progress over many years of decline, it would actually end up being a pretty big effect,” Dr. Nation said in an interview. “Small effect sizes could actually end up preventing a lot of cases of dementia,” he added.

The conflicting results in the BBB-crossing group – better verbal memory but worse attention ability – were “surprising,” he noted.

“I sort of didn’t believe it at first,” Dr. Nation said, “because the memory finding is sort of replication – we’d observed the same exact effect on memory in a smaller sample in another study. ... The attention [finding], going another way, was a new thing.”

Dr. Nation suggested that the intergroup differences in attention ability may stem from idiosyncrasies of the tests used to measure that domain, which can be impacted by cardiovascular or brain vascular disease. Or it could be caused by something else entirely, he said, noting that further investigation is needed.

He added that the improvements in verbal memory within the BBB-crossing group could be caused by direct effects on the brain. He pointed out that certain ACE polymorphisms have been linked with Alzheimer’s disease risk, and those same polymorphisms, in animal models, lead to neurodegeneration, with reversal possible through administration of ACE inhibitors.

“It could be that what we’re observing has nothing really to do with blood pressure,” Dr. Nation explained. “This could be a neuronal effect on learning memory systems.”

He went on to suggest that clinicians may consider these findings when selecting antihypertensive agents for their patients, with the caveat that all other prescribing factors have already been taking to account.

“In the event that you’re going to give an ACE inhibitor or an angiotensin receptor blocker anyway, and it ends up being a somewhat arbitrary decision in terms of which specific drug you’re going to give, then perhaps this is a piece of information you would take into account – that one gets in the brain and one doesn’t – in somebody at risk for cognitive decline,” Dr. Nation said.
 

Exact mechanisms of action unknown

Hélène Girouard, PhD, assistant professor of pharmacology and physiology at the University of Montreal, said in an interview that the findings are “of considerable importance, knowing that brain alterations could begin as much as 30 years before manifestation of dementia.”

Since 2003, Dr. Girouard has been studying the cognitive effects of antihypertensive medications. She noted that previous studies involving rodents “have shown beneficial effects [of BBB-crossing antihypertensive drugs] on cognition independent of their effects on blood pressure.”

The drugs’ exact mechanisms of action, however, remain elusive, according to Dr. Girouard, who offered several possible explanations, including amelioration of BBB disruption, brain inflammation, cerebral blood flow dysregulation, cholinergic dysfunction, and neurologic deficits. “Whether these mechanisms may explain Ho and colleagues’ observations remains to be established,” she added.

Andrea L. Schneider, MD, PhD, assistant professor of neurology at the University of Pennsylvania, Philadelphia, applauded the study, but ultimately suggested that more research is needed to impact clinical decision-making.

“The results of this important and well-done study suggest that further investigation into targeted mechanism-based approaches to selecting hypertension treatment agents, with a specific focus on cognitive outcomes, is warranted,” Dr. Schneider said in an interview. “Before changing clinical practice, further work is necessary to disentangle contributions of medication mechanism, comorbid vascular risk factors, and achieved blood pressure reduction, among others.”

The investigators disclosed support from the National Institutes of Health, the Alzheimer’s Association, the Waksman Foundation of Japan, and others. The interviewees reported no relevant conflicts of interest.

Antihypertensive medications that cross the blood-brain barrier (BBB) may be linked with less memory decline, compared with other drugs for high blood pressure, suggest the findings of a meta-analysis.

Over a 3-year period, cognitively normal older adults taking BBB-crossing antihypertensives demonstrated superior verbal memory, compared with similar individuals receiving non–BBB-crossing antihypertensives, reported lead author Jean K. Ho, PhD, of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, and colleagues.

According to the investigators, the findings add color to a known link between hypertension and neurologic degeneration, and may aid the search for new therapeutic targets.

“Hypertension is a well-established risk factor for cognitive decline and dementia, possibly through its effects on both cerebrovascular disease and Alzheimer’s disease,” Dr. Ho and colleagues wrote in Hypertension. “Studies of antihypertensive treatments have reported possible salutary effects on cognition and cerebrovascular disease, as well as Alzheimer’s disease neuropathology.”

In a previous study, individuals younger than 75 years exposed to antihypertensives had an 8% decreased risk of dementia per year of use, while another trial showed that intensive blood pressure–lowering therapy reduced mild cognitive impairment by 19%.

“Despite these encouraging findings ... larger meta-analytic studies have been hampered by the fact that pharmacokinetic properties are typically not considered in existing studies or routine clinical practice,” wrote Dr. Ho and colleagues. “The present study sought to fill this gap [in that it was] a large and longitudinal meta-analytic study of existing data recoded to assess the effects of BBB-crossing potential in renin-angiotensin system [RAS] treatments among hypertensive adults.”
 

Methods and results

The meta-analysis included randomized clinical trials, prospective cohort studies, and retrospective observational studies. The researchers assessed data on 12,849 individuals from 14 cohorts that received either BBB-crossing or non–BBB-crossing antihypertensives.

The BBB-crossing properties of RAS treatments were identified by a literature review. Of ACE inhibitors, captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as BBB crossing, and benazepril, enalapril, moexipril, and quinapril were classified as non–BBB-crossing. Of ARBs, telmisartan and candesartan were considered BBB-crossing, and olmesartan, eprosartan, irbesartan, and losartan were tagged as non–BBB-crossing.

Cognition was assessed via the following seven domains: executive function, attention, verbal memory learning, language, mental status, recall, and processing speed.

Compared with individuals taking non–BBB-crossing antihypertensives, those taking BBB-crossing agents had significantly superior verbal memory (recall), with a maximum effect size of 0.07 (P = .03).

According to the investigators, this finding was particularly noteworthy, as the BBB-crossing group had relatively higher vascular risk burden and lower mean education level.

“These differences make it all the more remarkable that the BBB-crossing group displayed better memory ability over time despite these cognitive disadvantages,” the investigators wrote.

Still, not all the findings favored BBB-crossing agents. Individuals in the BBB-crossing group had relatively inferior attention ability, with a minimum effect size of –0.17 (P = .02).

The other cognitive measures were not significantly different between groups.
 

Clinicians may consider findings after accounting for other factors

Principal investigator Daniel A. Nation, PhD, associate professor of psychological science and a faculty member of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, suggested that the small difference in verbal memory between groups could be clinically significant over a longer period of time.

“Although the overall effect size was pretty small, if you look at how long it would take for someone [with dementia] to progress over many years of decline, it would actually end up being a pretty big effect,” Dr. Nation said in an interview. “Small effect sizes could actually end up preventing a lot of cases of dementia,” he added.

The conflicting results in the BBB-crossing group – better verbal memory but worse attention ability – were “surprising,” he noted.

“I sort of didn’t believe it at first,” Dr. Nation said, “because the memory finding is sort of replication – we’d observed the same exact effect on memory in a smaller sample in another study. ... The attention [finding], going another way, was a new thing.”

Dr. Nation suggested that the intergroup differences in attention ability may stem from idiosyncrasies of the tests used to measure that domain, which can be impacted by cardiovascular or brain vascular disease. Or it could be caused by something else entirely, he said, noting that further investigation is needed.

He added that the improvements in verbal memory within the BBB-crossing group could be caused by direct effects on the brain. He pointed out that certain ACE polymorphisms have been linked with Alzheimer’s disease risk, and those same polymorphisms, in animal models, lead to neurodegeneration, with reversal possible through administration of ACE inhibitors.

“It could be that what we’re observing has nothing really to do with blood pressure,” Dr. Nation explained. “This could be a neuronal effect on learning memory systems.”

He went on to suggest that clinicians may consider these findings when selecting antihypertensive agents for their patients, with the caveat that all other prescribing factors have already been taking to account.

“In the event that you’re going to give an ACE inhibitor or an angiotensin receptor blocker anyway, and it ends up being a somewhat arbitrary decision in terms of which specific drug you’re going to give, then perhaps this is a piece of information you would take into account – that one gets in the brain and one doesn’t – in somebody at risk for cognitive decline,” Dr. Nation said.
 

Exact mechanisms of action unknown

Hélène Girouard, PhD, assistant professor of pharmacology and physiology at the University of Montreal, said in an interview that the findings are “of considerable importance, knowing that brain alterations could begin as much as 30 years before manifestation of dementia.”

Since 2003, Dr. Girouard has been studying the cognitive effects of antihypertensive medications. She noted that previous studies involving rodents “have shown beneficial effects [of BBB-crossing antihypertensive drugs] on cognition independent of their effects on blood pressure.”

The drugs’ exact mechanisms of action, however, remain elusive, according to Dr. Girouard, who offered several possible explanations, including amelioration of BBB disruption, brain inflammation, cerebral blood flow dysregulation, cholinergic dysfunction, and neurologic deficits. “Whether these mechanisms may explain Ho and colleagues’ observations remains to be established,” she added.

Andrea L. Schneider, MD, PhD, assistant professor of neurology at the University of Pennsylvania, Philadelphia, applauded the study, but ultimately suggested that more research is needed to impact clinical decision-making.

“The results of this important and well-done study suggest that further investigation into targeted mechanism-based approaches to selecting hypertension treatment agents, with a specific focus on cognitive outcomes, is warranted,” Dr. Schneider said in an interview. “Before changing clinical practice, further work is necessary to disentangle contributions of medication mechanism, comorbid vascular risk factors, and achieved blood pressure reduction, among others.”

The investigators disclosed support from the National Institutes of Health, the Alzheimer’s Association, the Waksman Foundation of Japan, and others. The interviewees reported no relevant conflicts of interest.

Patients with obesity who underwent bariatric surgery had 46% lower odds of stroke 1 year later, similar odds of stroke 3 years later, and 22% lower odds of stroke 5 years later, compared with matched control patients, in new research.

purestock/Thinkstock

Michael D. Williams, MD, presented the study findings (abstract A002) at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings are “very good news,” even though the protection against stroke declined further out from the surgery, John D. Scott, MD, scientific program chair of the ASMBS meeting, told this news organization.

The investigators matched more than 56,000 patients with obesity who had bariatric surgery with an equal number of similar patients who did not have this surgery, from a large national insurance database, in what they believe is the largest study of this to date.

“Any intervention that decreases your risk of [cardiovascular] events is good news,” said Dr. Scott, a clinical professor of surgery at the University of South Carolina, Greenville, and metabolic and bariatric surgery director at Prisma Health in Greenville, S.C. “And having a 22%-45% chance of reduction in stroke risk is a very worthwhile intervention.”

Asked how this would change the way clinicians inform patients of what to expect from bariatric surgery, he said: “I would advise patients that studies like this show that surgery would not increase your risk of having a stroke.

“This is consistent with many studies that show that the risks of all macrovascular events decrease after the comorbidity reductions seen after surgery.”

According to Dr. Scott, “the next steps might include a prospective randomized trial of medical treatment versus surgery alone for [cardiovascular]/stroke outcomes, but this is unlikely.”

Similarly, Dr. Williams told this news organization that “I would tell [patients] that surgery is an effective and durable method for weight loss. It also can improve comorbid conditions, particularly diabetes and hypertension.”

Even with this study, “I’m not sure it’s appropriate to say that bariatric surgery will reduce the risk of stroke,” he cautioned.

“However, as we continue to investigate the effects of bariatric surgery, this study contributes to the greater body of knowledge that suggests that reduction in ischemic stroke risk is yet another benefit of bariatric surgery.”

The assigned discussant, Corrigan L. McBride, MD, MBA wanted to know if the lower odds ratio at 1 year might be because preoperative patient selection might eliminate patients at high risk of poor cardiovascular outcomes.

Dr. Williams, a resident at Rush Medical College, Chicago, replied that it is difficult to eliminate potential selection bias, despite best efforts, but this study shows that he can tell patients: “Having surgery is not going to increases your risk of stroke.”

“This is an important study,” Dr. McBride, professor and chief of minimally invasive surgery and bariatric surgery, University of Nebraska Medical Center, Omaha, told this news organization.

“It is the first large study to show a decreased [or no increased] risk of stroke 1, 3, and 5 years after bariatric surgery compared to matched patients, and it had enough data to look at stroke as a standalone endpoint,” Dr. McBride said. “It is important too, for patients and their physicians to understand that there is a lower chance of them having a stroke if they have surgery than if they do not.”
 

‘Important,’ ‘good news’ for stroke risk after bariatric surgery

The impact of bariatric surgery on remission of type 2 diabetes is well known, Dr. Williams noted, and other studies have reported how bariatric surgery affects the risk of major adverse cardiovascular events – a composite of stroke, myocardial infarction, coronary artery disease, and all-cause death – including a study presented in the same meeting session.

However, a very large sample size is needed to be able to demonstrate the effect of bariatric surgery on stroke, since stroke is a rare event.

The researchers analyzed data from the Mariner (PearlDiver.) all-payer insurance national claims database of patients in the United States.

They matched 56,514 patients with a body mass index over 35 kg/m² and comorbidities or a BMI of more than 40 who underwent sleeve gastrectomy or Roux-en-Y gastric bypass during 2010-2019 with 56,514 control patients who did not undergo bariatric surgery.

A year after bariatric surgery, patients in that group had a lower stroke rate than patients in the control group (0.6% vs. 1.2%), and they had close to 50% lower odds of having a stroke (odds ratio, 0.54; 95% CI, 0.47-0.61).

Three years after bariatric surgery, there were 44,948 patients in each group; the rate of stroke was 2.1% in the surgery group and 2.2% in the control group, and there was no significant difference in the odds of having a stroke (OR, 0.96; 95% CI, 0.91-1.00).

Five years after bariatric surgery, there were 27,619 patients in each group; the stroke rate was lower in the bariatric surgery group than in the control group (2.8% vs 3.6%), but reduced odds of stroke was not as great as after 1 year (OR, 0.78; 95% CI, 0.65-0.90).

Dr. Williams has no relevant financial disclosures. Dr. McBride and Dr. Scott disclosed that they are speakers/trainers/faculty advisers for Gore. Dr. Scott is also a consultant for C-SATS (part of Johnson & Johnson).

Patients with obesity who underwent bariatric surgery had 46% lower odds of stroke 1 year later, similar odds of stroke 3 years later, and 22% lower odds of stroke 5 years later, compared with matched control patients, in new research.

purestock/Thinkstock

Michael D. Williams, MD, presented the study findings (abstract A002) at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings are “very good news,” even though the protection against stroke declined further out from the surgery, John D. Scott, MD, scientific program chair of the ASMBS meeting, told this news organization.

The investigators matched more than 56,000 patients with obesity who had bariatric surgery with an equal number of similar patients who did not have this surgery, from a large national insurance database, in what they believe is the largest study of this to date.

“Any intervention that decreases your risk of [cardiovascular] events is good news,” said Dr. Scott, a clinical professor of surgery at the University of South Carolina, Greenville, and metabolic and bariatric surgery director at Prisma Health in Greenville, S.C. “And having a 22%-45% chance of reduction in stroke risk is a very worthwhile intervention.”

Asked how this would change the way clinicians inform patients of what to expect from bariatric surgery, he said: “I would advise patients that studies like this show that surgery would not increase your risk of having a stroke.

“This is consistent with many studies that show that the risks of all macrovascular events decrease after the comorbidity reductions seen after surgery.”

According to Dr. Scott, “the next steps might include a prospective randomized trial of medical treatment versus surgery alone for [cardiovascular]/stroke outcomes, but this is unlikely.”

Similarly, Dr. Williams told this news organization that “I would tell [patients] that surgery is an effective and durable method for weight loss. It also can improve comorbid conditions, particularly diabetes and hypertension.”

Even with this study, “I’m not sure it’s appropriate to say that bariatric surgery will reduce the risk of stroke,” he cautioned.

“However, as we continue to investigate the effects of bariatric surgery, this study contributes to the greater body of knowledge that suggests that reduction in ischemic stroke risk is yet another benefit of bariatric surgery.”

The assigned discussant, Corrigan L. McBride, MD, MBA wanted to know if the lower odds ratio at 1 year might be because preoperative patient selection might eliminate patients at high risk of poor cardiovascular outcomes.

Dr. Williams, a resident at Rush Medical College, Chicago, replied that it is difficult to eliminate potential selection bias, despite best efforts, but this study shows that he can tell patients: “Having surgery is not going to increases your risk of stroke.”

“This is an important study,” Dr. McBride, professor and chief of minimally invasive surgery and bariatric surgery, University of Nebraska Medical Center, Omaha, told this news organization.

“It is the first large study to show a decreased [or no increased] risk of stroke 1, 3, and 5 years after bariatric surgery compared to matched patients, and it had enough data to look at stroke as a standalone endpoint,” Dr. McBride said. “It is important too, for patients and their physicians to understand that there is a lower chance of them having a stroke if they have surgery than if they do not.”
 

‘Important,’ ‘good news’ for stroke risk after bariatric surgery

The impact of bariatric surgery on remission of type 2 diabetes is well known, Dr. Williams noted, and other studies have reported how bariatric surgery affects the risk of major adverse cardiovascular events – a composite of stroke, myocardial infarction, coronary artery disease, and all-cause death – including a study presented in the same meeting session.

However, a very large sample size is needed to be able to demonstrate the effect of bariatric surgery on stroke, since stroke is a rare event.

The researchers analyzed data from the Mariner (PearlDiver.) all-payer insurance national claims database of patients in the United States.

They matched 56,514 patients with a body mass index over 35 kg/m² and comorbidities or a BMI of more than 40 who underwent sleeve gastrectomy or Roux-en-Y gastric bypass during 2010-2019 with 56,514 control patients who did not undergo bariatric surgery.

A year after bariatric surgery, patients in that group had a lower stroke rate than patients in the control group (0.6% vs. 1.2%), and they had close to 50% lower odds of having a stroke (odds ratio, 0.54; 95% CI, 0.47-0.61).

Three years after bariatric surgery, there were 44,948 patients in each group; the rate of stroke was 2.1% in the surgery group and 2.2% in the control group, and there was no significant difference in the odds of having a stroke (OR, 0.96; 95% CI, 0.91-1.00).

Five years after bariatric surgery, there were 27,619 patients in each group; the stroke rate was lower in the bariatric surgery group than in the control group (2.8% vs 3.6%), but reduced odds of stroke was not as great as after 1 year (OR, 0.78; 95% CI, 0.65-0.90).

Dr. Williams has no relevant financial disclosures. Dr. McBride and Dr. Scott disclosed that they are speakers/trainers/faculty advisers for Gore. Dr. Scott is also a consultant for C-SATS (part of Johnson & Johnson).

Patients with obesity who underwent bariatric surgery had 46% lower odds of stroke 1 year later, similar odds of stroke 3 years later, and 22% lower odds of stroke 5 years later, compared with matched control patients, in new research.

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Michael D. Williams, MD, presented the study findings (abstract A002) at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings are “very good news,” even though the protection against stroke declined further out from the surgery, John D. Scott, MD, scientific program chair of the ASMBS meeting, told this news organization.

The investigators matched more than 56,000 patients with obesity who had bariatric surgery with an equal number of similar patients who did not have this surgery, from a large national insurance database, in what they believe is the largest study of this to date.

“Any intervention that decreases your risk of [cardiovascular] events is good news,” said Dr. Scott, a clinical professor of surgery at the University of South Carolina, Greenville, and metabolic and bariatric surgery director at Prisma Health in Greenville, S.C. “And having a 22%-45% chance of reduction in stroke risk is a very worthwhile intervention.”

Asked how this would change the way clinicians inform patients of what to expect from bariatric surgery, he said: “I would advise patients that studies like this show that surgery would not increase your risk of having a stroke.

“This is consistent with many studies that show that the risks of all macrovascular events decrease after the comorbidity reductions seen after surgery.”

According to Dr. Scott, “the next steps might include a prospective randomized trial of medical treatment versus surgery alone for [cardiovascular]/stroke outcomes, but this is unlikely.”

Similarly, Dr. Williams told this news organization that “I would tell [patients] that surgery is an effective and durable method for weight loss. It also can improve comorbid conditions, particularly diabetes and hypertension.”

Even with this study, “I’m not sure it’s appropriate to say that bariatric surgery will reduce the risk of stroke,” he cautioned.

“However, as we continue to investigate the effects of bariatric surgery, this study contributes to the greater body of knowledge that suggests that reduction in ischemic stroke risk is yet another benefit of bariatric surgery.”

The assigned discussant, Corrigan L. McBride, MD, MBA wanted to know if the lower odds ratio at 1 year might be because preoperative patient selection might eliminate patients at high risk of poor cardiovascular outcomes.

Dr. Williams, a resident at Rush Medical College, Chicago, replied that it is difficult to eliminate potential selection bias, despite best efforts, but this study shows that he can tell patients: “Having surgery is not going to increases your risk of stroke.”

“This is an important study,” Dr. McBride, professor and chief of minimally invasive surgery and bariatric surgery, University of Nebraska Medical Center, Omaha, told this news organization.

“It is the first large study to show a decreased [or no increased] risk of stroke 1, 3, and 5 years after bariatric surgery compared to matched patients, and it had enough data to look at stroke as a standalone endpoint,” Dr. McBride said. “It is important too, for patients and their physicians to understand that there is a lower chance of them having a stroke if they have surgery than if they do not.”
 

‘Important,’ ‘good news’ for stroke risk after bariatric surgery

The impact of bariatric surgery on remission of type 2 diabetes is well known, Dr. Williams noted, and other studies have reported how bariatric surgery affects the risk of major adverse cardiovascular events – a composite of stroke, myocardial infarction, coronary artery disease, and all-cause death – including a study presented in the same meeting session.

However, a very large sample size is needed to be able to demonstrate the effect of bariatric surgery on stroke, since stroke is a rare event.

The researchers analyzed data from the Mariner (PearlDiver.) all-payer insurance national claims database of patients in the United States.

They matched 56,514 patients with a body mass index over 35 kg/m² and comorbidities or a BMI of more than 40 who underwent sleeve gastrectomy or Roux-en-Y gastric bypass during 2010-2019 with 56,514 control patients who did not undergo bariatric surgery.

A year after bariatric surgery, patients in that group had a lower stroke rate than patients in the control group (0.6% vs. 1.2%), and they had close to 50% lower odds of having a stroke (odds ratio, 0.54; 95% CI, 0.47-0.61).

Three years after bariatric surgery, there were 44,948 patients in each group; the rate of stroke was 2.1% in the surgery group and 2.2% in the control group, and there was no significant difference in the odds of having a stroke (OR, 0.96; 95% CI, 0.91-1.00).

Five years after bariatric surgery, there were 27,619 patients in each group; the stroke rate was lower in the bariatric surgery group than in the control group (2.8% vs 3.6%), but reduced odds of stroke was not as great as after 1 year (OR, 0.78; 95% CI, 0.65-0.90).

Dr. Williams has no relevant financial disclosures. Dr. McBride and Dr. Scott disclosed that they are speakers/trainers/faculty advisers for Gore. Dr. Scott is also a consultant for C-SATS (part of Johnson & Johnson).

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]