Cardiology

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

[email protected]

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

[email protected]

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

[email protected]

Music listening and singing each showed early, promising evidence for producing cardiovascular benefits, part of a burgeoning area of research that is exploring and documenting ways to effectively use music to improve health.

A study run at four centers in Italy randomized 159 patients with heart failure, primarily New York Heart Association class I or II disease, to either a daily regimen of at least 30 minutes spent listening to music daily or to a control group that received usual care with no music prescription. After 3 months, the 82 patients in the daily music-listening group had a statistically significant improvement in their Minnesota Living with Heart Failure Questionnaire scores, compared with 77 controls for the study’s primary outcome measure. The results also showed significant benefits, compared with placebo, for other, secondary efficacy measures including improvements in anxiety, depression, sleep quality, and cognition.

Although the results are considered preliminary, they drew significant attention when published in July 2020 (J Card Fail. 2020 Jul 1;26[7]:541-9), where it was accompanied by two editorials in the same issue as well as an editor’s statement. All these commentators as well as other experts interested in music as medicine gathered to further discuss the topic during a panel session at the virtual annual meeting of the Heart Failure Society of America.

Music as a calming influence

The source of the primary benefits seen in this Italian study likely involved “emotional, psychological, and relaxation,” suggested Jerome L. Fleg, MD, program officer for clinical cardiovascular disease at the National Heart, Lung, and Blood Institute in Bethesda, Md. Researchers had used calming potential as a major criterion when selecting the 80 classical pieces that the heart failure patients in the intervention arm of the study could shuffle on their play lists.

“The tempo/rhythm was set up in a range between 60 and 80 beats per minute, because this range mirrors the human heart rate and facilitates relaxation,” the investigators said in their published report. Unfortunately, noted Dr. Fleg, the study lacked physiologic and biomarker measurements that could have provided objective evidence of effects from music. And the study failed to include a control arm of patients instructed to spend 30 minutes a day resting and relaxing without instruction to listen to music, he noted.

Dr. Fleg had authored one of the July editorials, where he said “It is hoped that findings from these studies and others can expand the scientific evidence for music-based interventions and bring these therapies into clinical practice. The current study from Burrai et al. is a positive step in this direction for patients with heart failure.” (J Card Fail. 2020 Jul 1;26[7]: 550-1). What’s needed now, he added during the virtual session, are “more objective data” to better and more comprehensively document the benefits from a music-based intervention in patients with heart failure.
 

An add-on to standard care

The findings in heart failure patients follows a growing literature that’s shown music can generate a restful state by doing things like activating autonomic parasympathetic outflow while dampening sympathetic outflow. This produces moderation in mood and emotion as well as depressed heart rate, lowered blood pressure, and slowed respiration, commented Emmeline Edwards, PhD director of the division of extramural research of the National Center for Complementary and Integrative Health in Bethesda, Md. Music also seems able to stimulate higher-order brain regions that can result in reduced psychological stress, anxiety, and depression.

“It’s a promising protective intervention to add to standard care for cardiac patients,” Dr. Edwards said during the virtual session. “Music is part of the toolbox for managing symptoms and improving health and well-being.”

“Music is not a substitute for standard therapy, but could add to it,” declared Dr. Fleg.

The already-established intervention known as music therapy has identified music’s ability to modulate breathing as an important mediator of music’s effect.

“Breathing is one of the few physiological processes that can be voluntarily controlled making it a viable target for intervention,” noted opera soprano Renée Fleming and Sheri L. Robb, PhD, in the second editorial that accompanied the Italian heart failure report (J Card Fail. 2020 Jul 1;26[7]:552-4). The music-listening intervention “may have had more effect if they had used compositional features [of the music] to teach patients how to structure their breathing,” said Dr. Robb, a music therapist at Indiana University–Purdue University Indianapolis, during the virtual session.

Another variable to consider is the type of music. “What is the emotional response to the music, and how does that affect heart rate,” wondered Dr. Robb, a professor at the Indiana University School of Nursing in Indianapolis.

Music as exercise

The division that Dr. Edwards directs recently funded a pilot study that assessed the feasibility of using music to stimulate activity and improve breathing another way, by repurposing singing as a novel form of rehabilitative exercise.

The pilot study enrolled patients with coronary disease into a randomized study that tested whether a 14-minute session of supervised singing could produce acute improvement in vascular function, “a biomarker for the risk of future cardiovascular disease events,” explained Jacqueline P. Kulinski, MD, a preventive cardiologist at the Medical College of Wisconsin in Milwaukee. Dr. Kulinski did not report details of her yet-unpublished study, but said that her initial findings held promise for developing musical activities such as singing as a novel way to stimulate therapeutic physical activity in patients with heart disease.

“It’s exciting to see this signal” of benefit. “I envision music therapy as a part of cardiac rehabilitation, or an alternative for patients who can’t participate in traditional rehab,” Dr. Kulinski said during the virtual session. “I think of singing as a physical activity, as exercise, and using this exercise as medicine.”

Harmonizing with the NIH

“Singing is like swimming: You need to hold your breath,” agreed Ms. Fleming, who participated on the virtual panel and has spearheaded a collaboration between the National Institutes of Health and the Kennedy Center for the Performing Arts, the Sound Health Initiative, that’s coordinating research into the connections between music and health. Ms. Fleming helped launch the Sound Health Initiative in 2017 by coauthoring a JAMA article with the NIH director that spelled out the rationale and goals of the project (JAMA. 2017 Jun 27;317[24]:2470-1), and by launching a lecture tour on the topic in a presentation she calls Music and the Mind.

Andrew Eccles

Ms. Fleming has given her talk in more than 30 locations worldwide, and she’s found that “audiences love” the combination of neuroscience and music that her talks cover, she said. Her lectures highlight that, in addition to cardiovascular disease, the potential for music therapy and related interventions has been shown in patients with disorders that include autism, psychosis, pain, Parkinson’s disease, Alzheimer’s disease, and epilepsy.

The research highlighted in the session “opens new doors to prevention and treatment strategies using music for patients with heart failure and cardiovascular disease,” summed up Biykem Bozkurt, MD, professor of medicine at the Baylor College of Medicine in Houston and president of the Heart Failure Society of America, who helped organize the virtual session.

Dr. Fleg, Dr. Edwards, Dr. Robb, Dr Kulinski, Ms. Fleming, and Dr. Bozkurt had no relevant financial disclosures.
 

[email protected]
 

Music listening and singing each showed early, promising evidence for producing cardiovascular benefits, part of a burgeoning area of research that is exploring and documenting ways to effectively use music to improve health.

A study run at four centers in Italy randomized 159 patients with heart failure, primarily New York Heart Association class I or II disease, to either a daily regimen of at least 30 minutes spent listening to music daily or to a control group that received usual care with no music prescription. After 3 months, the 82 patients in the daily music-listening group had a statistically significant improvement in their Minnesota Living with Heart Failure Questionnaire scores, compared with 77 controls for the study’s primary outcome measure. The results also showed significant benefits, compared with placebo, for other, secondary efficacy measures including improvements in anxiety, depression, sleep quality, and cognition.

Although the results are considered preliminary, they drew significant attention when published in July 2020 (J Card Fail. 2020 Jul 1;26[7]:541-9), where it was accompanied by two editorials in the same issue as well as an editor’s statement. All these commentators as well as other experts interested in music as medicine gathered to further discuss the topic during a panel session at the virtual annual meeting of the Heart Failure Society of America.

Music as a calming influence

The source of the primary benefits seen in this Italian study likely involved “emotional, psychological, and relaxation,” suggested Jerome L. Fleg, MD, program officer for clinical cardiovascular disease at the National Heart, Lung, and Blood Institute in Bethesda, Md. Researchers had used calming potential as a major criterion when selecting the 80 classical pieces that the heart failure patients in the intervention arm of the study could shuffle on their play lists.

“The tempo/rhythm was set up in a range between 60 and 80 beats per minute, because this range mirrors the human heart rate and facilitates relaxation,” the investigators said in their published report. Unfortunately, noted Dr. Fleg, the study lacked physiologic and biomarker measurements that could have provided objective evidence of effects from music. And the study failed to include a control arm of patients instructed to spend 30 minutes a day resting and relaxing without instruction to listen to music, he noted.

Dr. Fleg had authored one of the July editorials, where he said “It is hoped that findings from these studies and others can expand the scientific evidence for music-based interventions and bring these therapies into clinical practice. The current study from Burrai et al. is a positive step in this direction for patients with heart failure.” (J Card Fail. 2020 Jul 1;26[7]: 550-1). What’s needed now, he added during the virtual session, are “more objective data” to better and more comprehensively document the benefits from a music-based intervention in patients with heart failure.
 

An add-on to standard care

The findings in heart failure patients follows a growing literature that’s shown music can generate a restful state by doing things like activating autonomic parasympathetic outflow while dampening sympathetic outflow. This produces moderation in mood and emotion as well as depressed heart rate, lowered blood pressure, and slowed respiration, commented Emmeline Edwards, PhD director of the division of extramural research of the National Center for Complementary and Integrative Health in Bethesda, Md. Music also seems able to stimulate higher-order brain regions that can result in reduced psychological stress, anxiety, and depression.

“It’s a promising protective intervention to add to standard care for cardiac patients,” Dr. Edwards said during the virtual session. “Music is part of the toolbox for managing symptoms and improving health and well-being.”

“Music is not a substitute for standard therapy, but could add to it,” declared Dr. Fleg.

The already-established intervention known as music therapy has identified music’s ability to modulate breathing as an important mediator of music’s effect.

“Breathing is one of the few physiological processes that can be voluntarily controlled making it a viable target for intervention,” noted opera soprano Renée Fleming and Sheri L. Robb, PhD, in the second editorial that accompanied the Italian heart failure report (J Card Fail. 2020 Jul 1;26[7]:552-4). The music-listening intervention “may have had more effect if they had used compositional features [of the music] to teach patients how to structure their breathing,” said Dr. Robb, a music therapist at Indiana University–Purdue University Indianapolis, during the virtual session.

Another variable to consider is the type of music. “What is the emotional response to the music, and how does that affect heart rate,” wondered Dr. Robb, a professor at the Indiana University School of Nursing in Indianapolis.

Music as exercise

The division that Dr. Edwards directs recently funded a pilot study that assessed the feasibility of using music to stimulate activity and improve breathing another way, by repurposing singing as a novel form of rehabilitative exercise.

The pilot study enrolled patients with coronary disease into a randomized study that tested whether a 14-minute session of supervised singing could produce acute improvement in vascular function, “a biomarker for the risk of future cardiovascular disease events,” explained Jacqueline P. Kulinski, MD, a preventive cardiologist at the Medical College of Wisconsin in Milwaukee. Dr. Kulinski did not report details of her yet-unpublished study, but said that her initial findings held promise for developing musical activities such as singing as a novel way to stimulate therapeutic physical activity in patients with heart disease.

“It’s exciting to see this signal” of benefit. “I envision music therapy as a part of cardiac rehabilitation, or an alternative for patients who can’t participate in traditional rehab,” Dr. Kulinski said during the virtual session. “I think of singing as a physical activity, as exercise, and using this exercise as medicine.”

Harmonizing with the NIH

“Singing is like swimming: You need to hold your breath,” agreed Ms. Fleming, who participated on the virtual panel and has spearheaded a collaboration between the National Institutes of Health and the Kennedy Center for the Performing Arts, the Sound Health Initiative, that’s coordinating research into the connections between music and health. Ms. Fleming helped launch the Sound Health Initiative in 2017 by coauthoring a JAMA article with the NIH director that spelled out the rationale and goals of the project (JAMA. 2017 Jun 27;317[24]:2470-1), and by launching a lecture tour on the topic in a presentation she calls Music and the Mind.

Andrew Eccles

Ms. Fleming has given her talk in more than 30 locations worldwide, and she’s found that “audiences love” the combination of neuroscience and music that her talks cover, she said. Her lectures highlight that, in addition to cardiovascular disease, the potential for music therapy and related interventions has been shown in patients with disorders that include autism, psychosis, pain, Parkinson’s disease, Alzheimer’s disease, and epilepsy.

The research highlighted in the session “opens new doors to prevention and treatment strategies using music for patients with heart failure and cardiovascular disease,” summed up Biykem Bozkurt, MD, professor of medicine at the Baylor College of Medicine in Houston and president of the Heart Failure Society of America, who helped organize the virtual session.

Dr. Fleg, Dr. Edwards, Dr. Robb, Dr Kulinski, Ms. Fleming, and Dr. Bozkurt had no relevant financial disclosures.
 

[email protected]
 

Music listening and singing each showed early, promising evidence for producing cardiovascular benefits, part of a burgeoning area of research that is exploring and documenting ways to effectively use music to improve health.

A study run at four centers in Italy randomized 159 patients with heart failure, primarily New York Heart Association class I or II disease, to either a daily regimen of at least 30 minutes spent listening to music daily or to a control group that received usual care with no music prescription. After 3 months, the 82 patients in the daily music-listening group had a statistically significant improvement in their Minnesota Living with Heart Failure Questionnaire scores, compared with 77 controls for the study’s primary outcome measure. The results also showed significant benefits, compared with placebo, for other, secondary efficacy measures including improvements in anxiety, depression, sleep quality, and cognition.

Although the results are considered preliminary, they drew significant attention when published in July 2020 (J Card Fail. 2020 Jul 1;26[7]:541-9), where it was accompanied by two editorials in the same issue as well as an editor’s statement. All these commentators as well as other experts interested in music as medicine gathered to further discuss the topic during a panel session at the virtual annual meeting of the Heart Failure Society of America.

Music as a calming influence

The source of the primary benefits seen in this Italian study likely involved “emotional, psychological, and relaxation,” suggested Jerome L. Fleg, MD, program officer for clinical cardiovascular disease at the National Heart, Lung, and Blood Institute in Bethesda, Md. Researchers had used calming potential as a major criterion when selecting the 80 classical pieces that the heart failure patients in the intervention arm of the study could shuffle on their play lists.

“The tempo/rhythm was set up in a range between 60 and 80 beats per minute, because this range mirrors the human heart rate and facilitates relaxation,” the investigators said in their published report. Unfortunately, noted Dr. Fleg, the study lacked physiologic and biomarker measurements that could have provided objective evidence of effects from music. And the study failed to include a control arm of patients instructed to spend 30 minutes a day resting and relaxing without instruction to listen to music, he noted.

Dr. Fleg had authored one of the July editorials, where he said “It is hoped that findings from these studies and others can expand the scientific evidence for music-based interventions and bring these therapies into clinical practice. The current study from Burrai et al. is a positive step in this direction for patients with heart failure.” (J Card Fail. 2020 Jul 1;26[7]: 550-1). What’s needed now, he added during the virtual session, are “more objective data” to better and more comprehensively document the benefits from a music-based intervention in patients with heart failure.
 

An add-on to standard care

The findings in heart failure patients follows a growing literature that’s shown music can generate a restful state by doing things like activating autonomic parasympathetic outflow while dampening sympathetic outflow. This produces moderation in mood and emotion as well as depressed heart rate, lowered blood pressure, and slowed respiration, commented Emmeline Edwards, PhD director of the division of extramural research of the National Center for Complementary and Integrative Health in Bethesda, Md. Music also seems able to stimulate higher-order brain regions that can result in reduced psychological stress, anxiety, and depression.

“It’s a promising protective intervention to add to standard care for cardiac patients,” Dr. Edwards said during the virtual session. “Music is part of the toolbox for managing symptoms and improving health and well-being.”

“Music is not a substitute for standard therapy, but could add to it,” declared Dr. Fleg.

The already-established intervention known as music therapy has identified music’s ability to modulate breathing as an important mediator of music’s effect.

“Breathing is one of the few physiological processes that can be voluntarily controlled making it a viable target for intervention,” noted opera soprano Renée Fleming and Sheri L. Robb, PhD, in the second editorial that accompanied the Italian heart failure report (J Card Fail. 2020 Jul 1;26[7]:552-4). The music-listening intervention “may have had more effect if they had used compositional features [of the music] to teach patients how to structure their breathing,” said Dr. Robb, a music therapist at Indiana University–Purdue University Indianapolis, during the virtual session.

Another variable to consider is the type of music. “What is the emotional response to the music, and how does that affect heart rate,” wondered Dr. Robb, a professor at the Indiana University School of Nursing in Indianapolis.

Music as exercise

The division that Dr. Edwards directs recently funded a pilot study that assessed the feasibility of using music to stimulate activity and improve breathing another way, by repurposing singing as a novel form of rehabilitative exercise.

The pilot study enrolled patients with coronary disease into a randomized study that tested whether a 14-minute session of supervised singing could produce acute improvement in vascular function, “a biomarker for the risk of future cardiovascular disease events,” explained Jacqueline P. Kulinski, MD, a preventive cardiologist at the Medical College of Wisconsin in Milwaukee. Dr. Kulinski did not report details of her yet-unpublished study, but said that her initial findings held promise for developing musical activities such as singing as a novel way to stimulate therapeutic physical activity in patients with heart disease.

“It’s exciting to see this signal” of benefit. “I envision music therapy as a part of cardiac rehabilitation, or an alternative for patients who can’t participate in traditional rehab,” Dr. Kulinski said during the virtual session. “I think of singing as a physical activity, as exercise, and using this exercise as medicine.”

Harmonizing with the NIH

“Singing is like swimming: You need to hold your breath,” agreed Ms. Fleming, who participated on the virtual panel and has spearheaded a collaboration between the National Institutes of Health and the Kennedy Center for the Performing Arts, the Sound Health Initiative, that’s coordinating research into the connections between music and health. Ms. Fleming helped launch the Sound Health Initiative in 2017 by coauthoring a JAMA article with the NIH director that spelled out the rationale and goals of the project (JAMA. 2017 Jun 27;317[24]:2470-1), and by launching a lecture tour on the topic in a presentation she calls Music and the Mind.

Andrew Eccles

Ms. Fleming has given her talk in more than 30 locations worldwide, and she’s found that “audiences love” the combination of neuroscience and music that her talks cover, she said. Her lectures highlight that, in addition to cardiovascular disease, the potential for music therapy and related interventions has been shown in patients with disorders that include autism, psychosis, pain, Parkinson’s disease, Alzheimer’s disease, and epilepsy.

The research highlighted in the session “opens new doors to prevention and treatment strategies using music for patients with heart failure and cardiovascular disease,” summed up Biykem Bozkurt, MD, professor of medicine at the Baylor College of Medicine in Houston and president of the Heart Failure Society of America, who helped organize the virtual session.

Dr. Fleg, Dr. Edwards, Dr. Robb, Dr Kulinski, Ms. Fleming, and Dr. Bozkurt had no relevant financial disclosures.
 

[email protected]
 

The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.

Catherine Hackett/MDedge News

Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
 

What DAPA-CKD means for heart failure

The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.

Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.

The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”

The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m²; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m².

“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
 

DAPA-CKD grows the pool of eligible heart failure patients

A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.

Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.

In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
 

New DAPA-HF results show no drug, device interactions

In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.

Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.

[email protected]

The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.

Catherine Hackett/MDedge News

Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
 

What DAPA-CKD means for heart failure

The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.

Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.

The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”

The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m²; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m².

“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
 

DAPA-CKD grows the pool of eligible heart failure patients

A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.

Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.

In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
 

New DAPA-HF results show no drug, device interactions

In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.

Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.

[email protected]

The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.

Catherine Hackett/MDedge News

Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
 

What DAPA-CKD means for heart failure

The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.

Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.

The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”

The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m²; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m².

“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
 

DAPA-CKD grows the pool of eligible heart failure patients

A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.

Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.

In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
 

New DAPA-HF results show no drug, device interactions

In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.

Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.

[email protected]

To protect the heart and kidneys, sodium-glucose transporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists should be considered for people with type 2 diabetes and chronic kidney disease (CKD), the American Heart Association advised in a new scientific statement.

Taken together, the results of relevant clinical trials indicate that SGLT2 inhibitors and GLP-1 receptor agonists safely and significantly reduce the risk for cardiovascular (CV) events, death, and the slow progression of CKD to end-stage kidney disease, including the risks for dialysis, transplantation, and death, the writing group says.

The scientific statement was published online Sept. 28 in Circulation.

“There has been rapid reporting of high-quality data in the cardio-renal-metabolic space with significant heart and kidney benefits, particularly with these two newer classes of antihyperglycemic agents,” Janani Rangaswami, MD, who chaired the writing group, said in an interview.

“More recent data show benefits in chronic kidney disease and heart failure even in patients without diabetes,” said Dr. Rangaswami, Einstein Medical Center and Sidney Kimmel Medical College, both in Philadelphia.

“These data are practice-changing in both cardiology and nephrology, and usher in a new era of disease-modifying therapies in heart and kidney disease,” Dr. Rangaswami added.
 

Recommendations at a glance

• Provide early and ongoing assessment of risks for CVD and CKD to patients who may benefit from SGLT2 inhibitors of GLP-1 receptor agonists.
• Tailor medication choices that meet the needs of individual patients. Realize that, given “consistent class-wide effects,” the choice of a specific SGLT2 inhibitor or GLP-1 receptor agonist may be dictated by affordability, coverage, and formulary considerations.
• Adjust all medications in tandem with these medicines and consider the burden of polypharmacy, which is common among people with type 2 diabetes. Adjust concomitant therapies and deprescribe where possible.
• Identify risks for hypoglycemia and educate patients on the signs so they can seek treatment quickly.
• Monitor and control high blood pressure.
• Counsel patients about the risks for and symptoms of euglycemic diabetic ketoacidosis when taking SGLT2 inhibitors, as well as classic DKA, which can be fatal.
• Regularly screen and counsel patients about foot care to prevent foot ulcers or blisters that can quickly become infected and lead to amputation.

The writing group identified two additional patient subgroups that may benefit from SGLT2 inhibitors and GLP-1 receptor agonists: those with heart failure with reduced ejection fraction with or without diabetes; and those with CKD who do not have diabetes. They say more data are anticipated to validate the use of SGLT2 inhibitors and GLP-1 receptor agonists in these “at-risk” patients.
 

Collaborative care model

The writing group proposed a collaborative care model, bridging cardiologists, nephrologists, endocrinologists, and primary care physicians, to help facilitate the “prompt and appropriate” integration of these new classes of medications in the management of patients with type 2 diabetes and CKD.

There is “an unmet need for a cardio-renal-metabolic care model that incorporates best practices in the real world to help align these therapies, especially with vulnerable high-risk patients with cardiorenal disease, and to overcome barriers toward uptake of these agents. Hopefully this statement provides some guidance to the cardiology and nephrology communities in that area,” Dr. Rangaswami said in an interview.

But old habits die hard, as research continues to show the slow adoption of these newer medications in the real world.

For example, a large observational study published last year showed a “striking” discordance between evidence-based, guideline-recommended use of SGLT2 inhibitors for the treatment of type 2 diabetes and their actual uptake in clinical practice.

Paradoxically, patients with CVD, heart failure, hypertension, CKD, and those at risk for hypoglycemia were less apt to receive an SGLT2 inhibitor than other patients.

“The relatively slow uptake of these agents is multifactorial,” Dr. Rangaswami said. “Cardiologists and nephrologists may suffer from some level of ‘therapeutic inertia’ when using new agents they are unfamiliar with and originally branded as ‘antidiabetic’ agents, with the perception of these agents being outside the scope of their practice.”

Two other factors are also at play. “The current health care system is based on ‘specialty silos,’ where specialists tend to stick to the traditional scope of their specialty and are reluctant to view these agents as part of their therapeutic armamentarium. Finally, insurance coverage barriers and affordability also limit the use on a widespread basis,” Dr. Rangaswami said.

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

To protect the heart and kidneys, sodium-glucose transporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists should be considered for people with type 2 diabetes and chronic kidney disease (CKD), the American Heart Association advised in a new scientific statement.

Taken together, the results of relevant clinical trials indicate that SGLT2 inhibitors and GLP-1 receptor agonists safely and significantly reduce the risk for cardiovascular (CV) events, death, and the slow progression of CKD to end-stage kidney disease, including the risks for dialysis, transplantation, and death, the writing group says.

The scientific statement was published online Sept. 28 in Circulation.

“There has been rapid reporting of high-quality data in the cardio-renal-metabolic space with significant heart and kidney benefits, particularly with these two newer classes of antihyperglycemic agents,” Janani Rangaswami, MD, who chaired the writing group, said in an interview.

“More recent data show benefits in chronic kidney disease and heart failure even in patients without diabetes,” said Dr. Rangaswami, Einstein Medical Center and Sidney Kimmel Medical College, both in Philadelphia.

“These data are practice-changing in both cardiology and nephrology, and usher in a new era of disease-modifying therapies in heart and kidney disease,” Dr. Rangaswami added.
 

Recommendations at a glance

• Provide early and ongoing assessment of risks for CVD and CKD to patients who may benefit from SGLT2 inhibitors of GLP-1 receptor agonists.
• Tailor medication choices that meet the needs of individual patients. Realize that, given “consistent class-wide effects,” the choice of a specific SGLT2 inhibitor or GLP-1 receptor agonist may be dictated by affordability, coverage, and formulary considerations.
• Adjust all medications in tandem with these medicines and consider the burden of polypharmacy, which is common among people with type 2 diabetes. Adjust concomitant therapies and deprescribe where possible.
• Identify risks for hypoglycemia and educate patients on the signs so they can seek treatment quickly.
• Monitor and control high blood pressure.
• Counsel patients about the risks for and symptoms of euglycemic diabetic ketoacidosis when taking SGLT2 inhibitors, as well as classic DKA, which can be fatal.
• Regularly screen and counsel patients about foot care to prevent foot ulcers or blisters that can quickly become infected and lead to amputation.

The writing group identified two additional patient subgroups that may benefit from SGLT2 inhibitors and GLP-1 receptor agonists: those with heart failure with reduced ejection fraction with or without diabetes; and those with CKD who do not have diabetes. They say more data are anticipated to validate the use of SGLT2 inhibitors and GLP-1 receptor agonists in these “at-risk” patients.
 

Collaborative care model

The writing group proposed a collaborative care model, bridging cardiologists, nephrologists, endocrinologists, and primary care physicians, to help facilitate the “prompt and appropriate” integration of these new classes of medications in the management of patients with type 2 diabetes and CKD.

There is “an unmet need for a cardio-renal-metabolic care model that incorporates best practices in the real world to help align these therapies, especially with vulnerable high-risk patients with cardiorenal disease, and to overcome barriers toward uptake of these agents. Hopefully this statement provides some guidance to the cardiology and nephrology communities in that area,” Dr. Rangaswami said in an interview.

But old habits die hard, as research continues to show the slow adoption of these newer medications in the real world.

For example, a large observational study published last year showed a “striking” discordance between evidence-based, guideline-recommended use of SGLT2 inhibitors for the treatment of type 2 diabetes and their actual uptake in clinical practice.

Paradoxically, patients with CVD, heart failure, hypertension, CKD, and those at risk for hypoglycemia were less apt to receive an SGLT2 inhibitor than other patients.

“The relatively slow uptake of these agents is multifactorial,” Dr. Rangaswami said. “Cardiologists and nephrologists may suffer from some level of ‘therapeutic inertia’ when using new agents they are unfamiliar with and originally branded as ‘antidiabetic’ agents, with the perception of these agents being outside the scope of their practice.”

Two other factors are also at play. “The current health care system is based on ‘specialty silos,’ where specialists tend to stick to the traditional scope of their specialty and are reluctant to view these agents as part of their therapeutic armamentarium. Finally, insurance coverage barriers and affordability also limit the use on a widespread basis,” Dr. Rangaswami said.

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

To protect the heart and kidneys, sodium-glucose transporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists should be considered for people with type 2 diabetes and chronic kidney disease (CKD), the American Heart Association advised in a new scientific statement.

Taken together, the results of relevant clinical trials indicate that SGLT2 inhibitors and GLP-1 receptor agonists safely and significantly reduce the risk for cardiovascular (CV) events, death, and the slow progression of CKD to end-stage kidney disease, including the risks for dialysis, transplantation, and death, the writing group says.

The scientific statement was published online Sept. 28 in Circulation.

“There has been rapid reporting of high-quality data in the cardio-renal-metabolic space with significant heart and kidney benefits, particularly with these two newer classes of antihyperglycemic agents,” Janani Rangaswami, MD, who chaired the writing group, said in an interview.

“More recent data show benefits in chronic kidney disease and heart failure even in patients without diabetes,” said Dr. Rangaswami, Einstein Medical Center and Sidney Kimmel Medical College, both in Philadelphia.

“These data are practice-changing in both cardiology and nephrology, and usher in a new era of disease-modifying therapies in heart and kidney disease,” Dr. Rangaswami added.
 

Recommendations at a glance

• Provide early and ongoing assessment of risks for CVD and CKD to patients who may benefit from SGLT2 inhibitors of GLP-1 receptor agonists.
• Tailor medication choices that meet the needs of individual patients. Realize that, given “consistent class-wide effects,” the choice of a specific SGLT2 inhibitor or GLP-1 receptor agonist may be dictated by affordability, coverage, and formulary considerations.
• Adjust all medications in tandem with these medicines and consider the burden of polypharmacy, which is common among people with type 2 diabetes. Adjust concomitant therapies and deprescribe where possible.
• Identify risks for hypoglycemia and educate patients on the signs so they can seek treatment quickly.
• Monitor and control high blood pressure.
• Counsel patients about the risks for and symptoms of euglycemic diabetic ketoacidosis when taking SGLT2 inhibitors, as well as classic DKA, which can be fatal.
• Regularly screen and counsel patients about foot care to prevent foot ulcers or blisters that can quickly become infected and lead to amputation.

The writing group identified two additional patient subgroups that may benefit from SGLT2 inhibitors and GLP-1 receptor agonists: those with heart failure with reduced ejection fraction with or without diabetes; and those with CKD who do not have diabetes. They say more data are anticipated to validate the use of SGLT2 inhibitors and GLP-1 receptor agonists in these “at-risk” patients.
 

Collaborative care model

The writing group proposed a collaborative care model, bridging cardiologists, nephrologists, endocrinologists, and primary care physicians, to help facilitate the “prompt and appropriate” integration of these new classes of medications in the management of patients with type 2 diabetes and CKD.

There is “an unmet need for a cardio-renal-metabolic care model that incorporates best practices in the real world to help align these therapies, especially with vulnerable high-risk patients with cardiorenal disease, and to overcome barriers toward uptake of these agents. Hopefully this statement provides some guidance to the cardiology and nephrology communities in that area,” Dr. Rangaswami said in an interview.

But old habits die hard, as research continues to show the slow adoption of these newer medications in the real world.

For example, a large observational study published last year showed a “striking” discordance between evidence-based, guideline-recommended use of SGLT2 inhibitors for the treatment of type 2 diabetes and their actual uptake in clinical practice.

Paradoxically, patients with CVD, heart failure, hypertension, CKD, and those at risk for hypoglycemia were less apt to receive an SGLT2 inhibitor than other patients.

“The relatively slow uptake of these agents is multifactorial,” Dr. Rangaswami said. “Cardiologists and nephrologists may suffer from some level of ‘therapeutic inertia’ when using new agents they are unfamiliar with and originally branded as ‘antidiabetic’ agents, with the perception of these agents being outside the scope of their practice.”

Two other factors are also at play. “The current health care system is based on ‘specialty silos,’ where specialists tend to stick to the traditional scope of their specialty and are reluctant to view these agents as part of their therapeutic armamentarium. Finally, insurance coverage barriers and affordability also limit the use on a widespread basis,” Dr. Rangaswami said.

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

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

I have been in practice for 31 years, so many of my patients are now in their 80s and 90s. Practices age with us, and I have been seeing many of these patients for 25-30 years. I have three rules I try to encourage my elderly patients follow, and I wanted to share them with you.

Absolutely, positively make sure you move!

Our older patients often have many reasons not to move, including pain from arthritis, deconditioning, muscle weakness, fatigue, and depression. “Keeping moving” is probably the most important thing a patient can do for their health.

Holme and Anderssen studied a large cohort of men for cardiovascular risk in 1972 and again in 2000. The surviving men were followed over an additional 12 years.¹ They found that 30 minutes of physical activity 6 days a week was associated with a 40% reduction in mortality. Sedentary men had a reduced life expectancy of about 5 years, compared with men who were moderately to vigorously physically active.

Stewart etal. studied the benefit of physical activity in people with stable coronary disease.² They concluded that, in patients with stable coronary heart disease, more physical activity was associated with lower mortality, and the largest benefit occurred in the sedentary patient groups and the highest cardiac risk groups.

Saint-Maurice et al. studied the effects of total daily step count and step intensity on mortality risk.³ They found that the risk of all-cause mortality decreases as the total number of daily steps increases, but that the speed of those steps did not make a difference. This is very encouraging data for our elderly patients. Moving is the secret, even if it may not be moving at a fast pace!
 

Never, ever get on a ladder!

This one should be part of every geriatric’s assessment and every Medicare wellness exam. I first experienced the horror of what can happen when elderly people climb when a 96-year-old healthy patient of mine fell off his roof and died. I never thought to tell him climbing on the roof was an awful idea.

Akland et al. looked at the epidemiology and outcomes of ladder-related falls that required ICU admission.⁴ Hospital mortality was 26%, and almost all of the mortalities occurred in older males in domestic falls, who died as a result of traumatic brain injury. Fewer than half of the survivors were living independently 1 year after the fall.

Valmuur et al. studied ladder related falls in Australia.⁵ They found that rates of ladder related falls requiring hospitalization rose from about 20/100,000 for men ages 15-29 years to 78/100,000 for men aged over 60 years. Of those who died from fall-related injury, 82% were over the age of 60, with more than 70% dying from head injuries.

Schaffarczyk et al. looked at the impact of nonoccupational falls from ladders in men aged over 50 years.⁶ The mean age of the patients in the study was 64 years (range, 50-85), with 27% suffering severe trauma. There was a striking impact on long-term function occurring in over half the study patients. The authors did interviews with patients in follow-up long after the falls and found that most never thought of themselves at risk for a fall, and after the experience of a bad fall, would never consider going on a ladder again. I think it is important for health care professionals to discuss the dangers of ladder use with our older patients, pointing out the higher risk of falling and the potential for the fall to be a life-changing or life-ending event.
 

Let them eat!

Many patients have a reduced appetite as they age. We work hard with our patients to choose a healthy diet throughout their lives, to help ward off obesity, treat hypertension, prevent or control diabetes, or provide heart health. Many patients just stop being interested in food, reduce intake, and may lose weight and muscle mass. When my patients pass the age of 85, I change my focus to encouraging them to eat for calories, socialization, and joy. I think the marginal benefits of more restrictive diets are small, compared with the benefits of helping your patients enjoy eating again. I ask patients what their very favorite foods are and encourage them to have them.

Pearl

Keep your patients eating and moving, except not onto a ladder!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Holme I, Anderssen SA. Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow-up of the Oslo II study. Br J Sports Med. 2015; 49:743-8.

2. Stewart RAH et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017 Oct 3;70(14):1689-1700..

3. Saint-Maurice PF et al. Association of daily step count and step intensity with mortality among U.S. adults. JAMA 2020;323:1151-60.

4. Ackland HM et al. Danger at every rung: Epidemiology and outcomes of ICU-admitted ladder-related trauma. Injury. 2016;47:1109-117.

5. Vallmuur K et al. Falls from ladders in Australia: comparing occupational and nonoccupational injuries across age groups. Aust N Z J Public Health. 2016 Dec;40(6):559-63.

6. Schaffarczyk K et al. Nonoccupational falls from ladders in men 50 years and over: Contributing factors and impact. Injury. 2020 Aug;51(8):1798-1804.

Jun Yang, MBBS, had watched as her father, who had battled hypertension for decades, ended up on four medications that still couldn’t bring his blood pressure to a healthy level. The cardiovascular endocrinologist then ran some tests, and soon thereafter her father had his blood pressure optimized on just one targeted medication.

Courtesy Dr. Jun Yang

Dr. Yang’s father was found to have a hormonal condition known as primary aldosteronism (PA) as the cause of his hypertension.

It turns out that PA is not as rare as once thought.

An eye-catching report in Annals of Internal Medicine this spring of an unexpectedly high prevalence of primary aldosteronism among a diverse cross section of U.S. patients with hypertension has raised issues that could dramatically change the way doctors in America, and elsewhere, assess and manage high blood pressure.

Foremost is the question of whether primary care physicians – the clinicians at the front line for diagnosing and initially treating most patients with hypertension – will absorb and act on this new evidence. For them, aldosteronism doesn’t automatically come to mind when they see high numbers on a BP monitor, and yet this latest research found that up to a third of all 726 patients in the study who were diagnosed with hypertension and with high urinary salt levels had PA.

That translates to a roughly three- to fivefold increase over standard prevalence estimates, and is a ”game changer” for how clinicians should approach hypertension management and PA diagnosis going forward, said John W. Funder, MD, in an editorial accompanying the Annals study.

Long considered relatively uncommon, hypertension driven by an excess of the hormone aldosterone, often because of an adenoma on the adrenal gland, is not the same as conventional “essential” hypertension. The former benefits from early diagnosis because its treatment is completely different – close to half of all PA patients can be treated definitively and quickly with surgical removal of an adenoma from one side of the adrenal gland.

For other PA patients, who have bilateral adrenal hyperplasia that is impossible to resolve surgically, treatment with drugs called mineralocorticoid receptor antagonists (MRAs), such as spironolactone, is needed because they target the hormonal cause of the high BP.

But what usually happens is that a patient with PA is mistakenly diagnosed with essential hypertension, in which the classic approach to treatment is to start with one regular antihypertensive drug, and add on further ones from different drug classes if blood pressure is not adequately controlled. When patients are taking three drugs, without adequate control, they are labeled as having “resistant hypertension.”

But in the case of PA, none of these conventional antihypertensives work, and the process of continuing to monitor and add different drugs wastes time, during which patients deteriorate.

“We need to change the culture of waiting for hypertension to be resistant and have patients riddled with end-organ damage,” due to years of persistently high BP and excess aldosterone “before we look for a secondary cause” like PA, declared Dr. Yang, of Hudson Institute of Medical Research and Monash University in Melbourne, during an interview.

So early diagnosis and prompt treatment of PA is key.

In addition to boosting the public health importance of early PA detection in hypertensive patients, the new up-sized PA prevalence numbers throw a spotlight on primary care physicians (PCPs) as key players who will need to apply the findings to practice on a public health scale.

These novel results create a need for “new guidelines, and a radically revised game plan with the key role of PCPs” emphasized in future management of patients with hypertension, said Dr. Funder, a professor of medicine at Monash University, in a second recent editorial in Hypertension.

“Buy-in by PCPs is essential,” agrees Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville, and a coauthor of the new study.

But he too acknowledges that this presents a major challenge. PCPs and internists, who diagnose a lot of hypertension, are “not used to thinking about aldosterone,” he said in an interview, encapsulating the key problem faced by proponents of earlier and more widespread PA assessment.

This dilemma looms as a “huge public health issue,” Dr. Carey warned.
 

‘We’re a long way from getting’ PCPs to buy in to PA screening

Will PCPs grow more comfortable with screening patients for PA themselves, or might they become more willing to refer hypertensive individuals for assessment at an expert center?

One skeptic is Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg. The finding about high PA prevalence in patients with hypertension “is brand new, [and] the message needs to get to PCPs,” he said. But, “We’re a long way from getting it” to them. “I don’t know how to do that. It will be a tough sell.”

In addition, repositioning MRAs as an earlier option for many hypertensive patients won’t be easy either, because “we’ll never have outcome-trial data for MRAs,” given that they are now generic drugs, he noted.

“No clinical trial data show [MRAs] are first-line drugs,” said Dr. Feldman, who explained that, instead, MRAs are considered “go-to drugs” for patients with treatment-resistant hypertension, a niche therapeutic area. Results from the PATHWAY-2 trial published 5 years ago in Lancet showed “spironolactone was clearly the most effective treatment for the condition,” according to the report authors.

But even among patients with resistant hypertension, screening for PA dramatically lags despite being enshrined in guidelines.

“PCPs should start checking aldosterone-to-renin ratios [a widely used PA screen] in all patients with resistant hypertension or hypertension with hypokalemia, and then refer patients to specialists for testing and management,” said Jordana B. Cohen, MD, a nephrologist and hypertension researcher at the University of Pennsylvania in Philadelphia.

But recent studies of U.S. patient populations with clinical characteristics that meet existing criteria for PA screening showed that just 1%-2% of these individuals underwent an initial PA assessment, she noted, citing reports in the journals Surgery and Hypertension.

“We need to prioritize improving screening in these high-risk patients,” she stressed in an interview.

This illustrates that, in some respects, the new prevalence numbers are beside the point, because PA has been going unscreened and overlooked far too often even in the context of historical, lower prevalence rates, said Dr. Yang.

“The key point is that approximately 1 in 10 people with hypertension, and even more with resistant hypertension, have a form of the disease that is worse than essential hypertension but is routinely missed at present” and is also highly treatable.

“Evidence for the need for increased awareness of PA has been building for 2 decades,” stressed Dr. Yang, who has coauthored several commentaries and reviews that have bemoaned PA’s underappreciated status.
 

Interest in partnering with PCPs on guidance grows

One potential solution is to have endocrinologists and hypertension specialists’ partner with PCPs to come up with diagnostic and management recommendations. Both Dr. Funder and Dr. Carey are opinion leaders regarding the role of aldosterone in hypertension, and both were coauthors of the 2016 Endocrine Society guideline for PA assessment and management published in the Journal of Clinical Endocrinology & Metabolism , with Dr. Funder chairing the writing panel.

Now approaching its fifth year in effect, this guideline is “due for revision,” and “my hope is that we’ll be able to partner with one or more PCP organizations to come up with a version of the guideline targeted to PCPs,” Dr. Carey said.

He voiced interest in working on this with the American College of Physicians, which represents U.S. internal medicine physicians, and the American Academy of Family Physicians.

“We definitely need a partnership and educational efforts to get the word out from these organizations and not from a specialty society,” said Dr. Carey.

Dr. Funder said he has submitted a proposal to the Endocrine Society for a guidelines update he would chair with Dr. Carey’s assistance and with a diverse writing group that includes PCPs. Dr. Carey said that ideally this panel would write and release a revised guideline in 2021.

“Several of us are chomping at the bit to get this done,” he noted.

But participation by the ACP and AAFP remain uncertain as of September 2020. When approached about this, an ACP spokesperson said the organization had no comment. A spokesperson for the AAFP said, “It’s too early to tell if we will partner with any other organizations to develop guidelines specific to excess aldosterone, and how such guidelines might be received by our members.”

Recent history shows little cooperation between ACP, AAFP, and what might be termed the U.S. hypertension “establishment.” For example, when the American College of Cardiology and the American Heart Association released their most recent essential hypertension management guidelines in Hypertension in 2018, it was never adopted by ACP or AAFP.

The latter two organizations continue to endorse a higher BP threshold for diagnosing hypertension, and higher treatment targets set by alternative expert panels to those of the AHA/ACC.
 

Collaboration feasible, although PCPs overworked

Dr. Carey hopes that this episode will not preclude agreement over PA screening.

“I think it is still possible to partner with [the ACP and AAFP],” he observed, adding that he believes high PA prevalence among hypertensive patients and its consequences when unrecognized is “noncontentious.”

But he acknowledges that other, substantial hurdles also exist, notably the “overwhelming workload” that American PCPs already face.

David O’Gurek, MD, a family and community medicine physician at the Lewis Katz School of Medicine of Temple University in Philadelphia, agrees that a revamped approach to PA screening developed cooperatively between PCPs and specialists is an important goal and potentially feasible despite prior disagreements. “There has to be room for collaboration,” he said, but also emphasized the need for developing policies based on a systematic evidence review and a focus on patient-centered outcomes.

“We’re certainly missing patients with PA, but there needs to be greater clarity and standardization about the most appropriate screening approach and cutoff level” for flagging patients who need specialized assessment, Dr. O’Gurek said in an interview.

The current endocrinology literature also shows that experts remain divided on how best to accomplish this.

And some hypertension specialists question whether existing evidence is conclusive enough to warrant revised guidelines.

Dr. Cohen, the nephrologist and hypertension researcher, said that, while the recent prevalence report in Annals of Internal Medicine is “intriguing, hypothesis-generating information that suggests we are missing many cases of hyperaldosteronism in routine care,” she nevertheless believes that “we need additional data to be able to truly understand the breadth and implications of the findings.”

William C. Cushman, MD, a hypertension management specialist at the University of Tennessee Health Science Center in Memphis, agrees.

Changing existing practice guidelines “really needs randomized, controlled trials demonstrating a difference in long-term outcomes, ideally major cardiovascular outcomes,” that result from broader PA screening, he said.

Dr. Carey concurs that more evidence is needed to confirm the Annals report, but is confident this evidence will be in hand by the time a guideline-revision panel meets in 2021.
 

Australian model of PCPs screening for PA could be implemented in United States

An example of what might be possible when PCPs, endocrinologists, and hypertension specialists work together to make PA screening more accessible can be found in Melbourne, at the Endocrine Hypertension Service of Monash Health, in association with the Hudson Institute of Medical Research.

This began operating in July 2016, cofounded by Dr. Yang, whose experiences with her own father made her sensitive to the issue.

The service’s aim is to “address the underdiagnosis of PA, and to offer a streamlined diagnostic service for patients with hypertension,” with an “extensive outreach program” targeted to regional PCPs that, among other messages, encourages them to screen patients for PA when blood pressures exceed 140/90 mm Hg.

During its first 3 years of operation, the service saw 267 patients, with PA diagnosed in 135 and ruled out in 73 patients.

Notably, the proportion of these patients referred from PCPs jumped from 21% of 70 patients during the first year of operation to 47% of 70 patients during year 2, and 52% of 127 patients during the third year, ending in July 2019, said Dr. Yang, who continues to help run the service.

During the first year, a scant 3% of referred patients had recently diagnosed hypertension, but this rose to 14% during the second year, and to 19% during the most recent year with data available.

The median duration of diagnosed hypertension among referred patients fell from 11 years during year 1, to 7 years during year 3.

Service clinicians diagnosed 37 patients with unilateral adenomas, and removed them from 23 patients with four more awaiting surgery and the remaining 10 opting instead for medical management. Another 95 patients went on therapy with a MRA, and during the most recent year studied all patients who began a MRA regimen had a partial or complete clinical response.

Dr. Carey said the “creative program represents a model for implementation in U.S. practice.

Dr. Funder, Dr. Carey, Dr. Feldman, Dr. Yang, Dr. Cohen, and Dr. O’Gurek had no relevant disclosures. Dr. Cushman has been a consultant to Novartis, received personal fees from Sanofi, and research funding from Eli Lilly.

[email protected]

Jun Yang, MBBS, had watched as her father, who had battled hypertension for decades, ended up on four medications that still couldn’t bring his blood pressure to a healthy level. The cardiovascular endocrinologist then ran some tests, and soon thereafter her father had his blood pressure optimized on just one targeted medication.

Courtesy Dr. Jun Yang

Dr. Yang’s father was found to have a hormonal condition known as primary aldosteronism (PA) as the cause of his hypertension.

It turns out that PA is not as rare as once thought.

An eye-catching report in Annals of Internal Medicine this spring of an unexpectedly high prevalence of primary aldosteronism among a diverse cross section of U.S. patients with hypertension has raised issues that could dramatically change the way doctors in America, and elsewhere, assess and manage high blood pressure.

Foremost is the question of whether primary care physicians – the clinicians at the front line for diagnosing and initially treating most patients with hypertension – will absorb and act on this new evidence. For them, aldosteronism doesn’t automatically come to mind when they see high numbers on a BP monitor, and yet this latest research found that up to a third of all 726 patients in the study who were diagnosed with hypertension and with high urinary salt levels had PA.

That translates to a roughly three- to fivefold increase over standard prevalence estimates, and is a ”game changer” for how clinicians should approach hypertension management and PA diagnosis going forward, said John W. Funder, MD, in an editorial accompanying the Annals study.

Long considered relatively uncommon, hypertension driven by an excess of the hormone aldosterone, often because of an adenoma on the adrenal gland, is not the same as conventional “essential” hypertension. The former benefits from early diagnosis because its treatment is completely different – close to half of all PA patients can be treated definitively and quickly with surgical removal of an adenoma from one side of the adrenal gland.

For other PA patients, who have bilateral adrenal hyperplasia that is impossible to resolve surgically, treatment with drugs called mineralocorticoid receptor antagonists (MRAs), such as spironolactone, is needed because they target the hormonal cause of the high BP.

But what usually happens is that a patient with PA is mistakenly diagnosed with essential hypertension, in which the classic approach to treatment is to start with one regular antihypertensive drug, and add on further ones from different drug classes if blood pressure is not adequately controlled. When patients are taking three drugs, without adequate control, they are labeled as having “resistant hypertension.”

But in the case of PA, none of these conventional antihypertensives work, and the process of continuing to monitor and add different drugs wastes time, during which patients deteriorate.

“We need to change the culture of waiting for hypertension to be resistant and have patients riddled with end-organ damage,” due to years of persistently high BP and excess aldosterone “before we look for a secondary cause” like PA, declared Dr. Yang, of Hudson Institute of Medical Research and Monash University in Melbourne, during an interview.

So early diagnosis and prompt treatment of PA is key.

In addition to boosting the public health importance of early PA detection in hypertensive patients, the new up-sized PA prevalence numbers throw a spotlight on primary care physicians (PCPs) as key players who will need to apply the findings to practice on a public health scale.

These novel results create a need for “new guidelines, and a radically revised game plan with the key role of PCPs” emphasized in future management of patients with hypertension, said Dr. Funder, a professor of medicine at Monash University, in a second recent editorial in Hypertension.

“Buy-in by PCPs is essential,” agrees Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville, and a coauthor of the new study.

But he too acknowledges that this presents a major challenge. PCPs and internists, who diagnose a lot of hypertension, are “not used to thinking about aldosterone,” he said in an interview, encapsulating the key problem faced by proponents of earlier and more widespread PA assessment.

This dilemma looms as a “huge public health issue,” Dr. Carey warned.
 

‘We’re a long way from getting’ PCPs to buy in to PA screening

Will PCPs grow more comfortable with screening patients for PA themselves, or might they become more willing to refer hypertensive individuals for assessment at an expert center?

One skeptic is Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg. The finding about high PA prevalence in patients with hypertension “is brand new, [and] the message needs to get to PCPs,” he said. But, “We’re a long way from getting it” to them. “I don’t know how to do that. It will be a tough sell.”

In addition, repositioning MRAs as an earlier option for many hypertensive patients won’t be easy either, because “we’ll never have outcome-trial data for MRAs,” given that they are now generic drugs, he noted.

“No clinical trial data show [MRAs] are first-line drugs,” said Dr. Feldman, who explained that, instead, MRAs are considered “go-to drugs” for patients with treatment-resistant hypertension, a niche therapeutic area. Results from the PATHWAY-2 trial published 5 years ago in Lancet showed “spironolactone was clearly the most effective treatment for the condition,” according to the report authors.

But even among patients with resistant hypertension, screening for PA dramatically lags despite being enshrined in guidelines.

“PCPs should start checking aldosterone-to-renin ratios [a widely used PA screen] in all patients with resistant hypertension or hypertension with hypokalemia, and then refer patients to specialists for testing and management,” said Jordana B. Cohen, MD, a nephrologist and hypertension researcher at the University of Pennsylvania in Philadelphia.

But recent studies of U.S. patient populations with clinical characteristics that meet existing criteria for PA screening showed that just 1%-2% of these individuals underwent an initial PA assessment, she noted, citing reports in the journals Surgery and Hypertension.

“We need to prioritize improving screening in these high-risk patients,” she stressed in an interview.

This illustrates that, in some respects, the new prevalence numbers are beside the point, because PA has been going unscreened and overlooked far too often even in the context of historical, lower prevalence rates, said Dr. Yang.

“The key point is that approximately 1 in 10 people with hypertension, and even more with resistant hypertension, have a form of the disease that is worse than essential hypertension but is routinely missed at present” and is also highly treatable.

“Evidence for the need for increased awareness of PA has been building for 2 decades,” stressed Dr. Yang, who has coauthored several commentaries and reviews that have bemoaned PA’s underappreciated status.
 

Interest in partnering with PCPs on guidance grows

One potential solution is to have endocrinologists and hypertension specialists’ partner with PCPs to come up with diagnostic and management recommendations. Both Dr. Funder and Dr. Carey are opinion leaders regarding the role of aldosterone in hypertension, and both were coauthors of the 2016 Endocrine Society guideline for PA assessment and management published in the Journal of Clinical Endocrinology & Metabolism , with Dr. Funder chairing the writing panel.

Now approaching its fifth year in effect, this guideline is “due for revision,” and “my hope is that we’ll be able to partner with one or more PCP organizations to come up with a version of the guideline targeted to PCPs,” Dr. Carey said.

He voiced interest in working on this with the American College of Physicians, which represents U.S. internal medicine physicians, and the American Academy of Family Physicians.

“We definitely need a partnership and educational efforts to get the word out from these organizations and not from a specialty society,” said Dr. Carey.

Dr. Funder said he has submitted a proposal to the Endocrine Society for a guidelines update he would chair with Dr. Carey’s assistance and with a diverse writing group that includes PCPs. Dr. Carey said that ideally this panel would write and release a revised guideline in 2021.

“Several of us are chomping at the bit to get this done,” he noted.

But participation by the ACP and AAFP remain uncertain as of September 2020. When approached about this, an ACP spokesperson said the organization had no comment. A spokesperson for the AAFP said, “It’s too early to tell if we will partner with any other organizations to develop guidelines specific to excess aldosterone, and how such guidelines might be received by our members.”

Recent history shows little cooperation between ACP, AAFP, and what might be termed the U.S. hypertension “establishment.” For example, when the American College of Cardiology and the American Heart Association released their most recent essential hypertension management guidelines in Hypertension in 2018, it was never adopted by ACP or AAFP.

The latter two organizations continue to endorse a higher BP threshold for diagnosing hypertension, and higher treatment targets set by alternative expert panels to those of the AHA/ACC.
 

Collaboration feasible, although PCPs overworked

Dr. Carey hopes that this episode will not preclude agreement over PA screening.

“I think it is still possible to partner with [the ACP and AAFP],” he observed, adding that he believes high PA prevalence among hypertensive patients and its consequences when unrecognized is “noncontentious.”

But he acknowledges that other, substantial hurdles also exist, notably the “overwhelming workload” that American PCPs already face.

David O’Gurek, MD, a family and community medicine physician at the Lewis Katz School of Medicine of Temple University in Philadelphia, agrees that a revamped approach to PA screening developed cooperatively between PCPs and specialists is an important goal and potentially feasible despite prior disagreements. “There has to be room for collaboration,” he said, but also emphasized the need for developing policies based on a systematic evidence review and a focus on patient-centered outcomes.

“We’re certainly missing patients with PA, but there needs to be greater clarity and standardization about the most appropriate screening approach and cutoff level” for flagging patients who need specialized assessment, Dr. O’Gurek said in an interview.

The current endocrinology literature also shows that experts remain divided on how best to accomplish this.

And some hypertension specialists question whether existing evidence is conclusive enough to warrant revised guidelines.

Dr. Cohen, the nephrologist and hypertension researcher, said that, while the recent prevalence report in Annals of Internal Medicine is “intriguing, hypothesis-generating information that suggests we are missing many cases of hyperaldosteronism in routine care,” she nevertheless believes that “we need additional data to be able to truly understand the breadth and implications of the findings.”

William C. Cushman, MD, a hypertension management specialist at the University of Tennessee Health Science Center in Memphis, agrees.

Changing existing practice guidelines “really needs randomized, controlled trials demonstrating a difference in long-term outcomes, ideally major cardiovascular outcomes,” that result from broader PA screening, he said.

Dr. Carey concurs that more evidence is needed to confirm the Annals report, but is confident this evidence will be in hand by the time a guideline-revision panel meets in 2021.
 

Australian model of PCPs screening for PA could be implemented in United States

An example of what might be possible when PCPs, endocrinologists, and hypertension specialists work together to make PA screening more accessible can be found in Melbourne, at the Endocrine Hypertension Service of Monash Health, in association with the Hudson Institute of Medical Research.

This began operating in July 2016, cofounded by Dr. Yang, whose experiences with her own father made her sensitive to the issue.

The service’s aim is to “address the underdiagnosis of PA, and to offer a streamlined diagnostic service for patients with hypertension,” with an “extensive outreach program” targeted to regional PCPs that, among other messages, encourages them to screen patients for PA when blood pressures exceed 140/90 mm Hg.

During its first 3 years of operation, the service saw 267 patients, with PA diagnosed in 135 and ruled out in 73 patients.

Notably, the proportion of these patients referred from PCPs jumped from 21% of 70 patients during the first year of operation to 47% of 70 patients during year 2, and 52% of 127 patients during the third year, ending in July 2019, said Dr. Yang, who continues to help run the service.

During the first year, a scant 3% of referred patients had recently diagnosed hypertension, but this rose to 14% during the second year, and to 19% during the most recent year with data available.

The median duration of diagnosed hypertension among referred patients fell from 11 years during year 1, to 7 years during year 3.

Service clinicians diagnosed 37 patients with unilateral adenomas, and removed them from 23 patients with four more awaiting surgery and the remaining 10 opting instead for medical management. Another 95 patients went on therapy with a MRA, and during the most recent year studied all patients who began a MRA regimen had a partial or complete clinical response.

Dr. Carey said the “creative program represents a model for implementation in U.S. practice.

Dr. Funder, Dr. Carey, Dr. Feldman, Dr. Yang, Dr. Cohen, and Dr. O’Gurek had no relevant disclosures. Dr. Cushman has been a consultant to Novartis, received personal fees from Sanofi, and research funding from Eli Lilly.

[email protected]

Jun Yang, MBBS, had watched as her father, who had battled hypertension for decades, ended up on four medications that still couldn’t bring his blood pressure to a healthy level. The cardiovascular endocrinologist then ran some tests, and soon thereafter her father had his blood pressure optimized on just one targeted medication.

Courtesy Dr. Jun Yang

Dr. Yang’s father was found to have a hormonal condition known as primary aldosteronism (PA) as the cause of his hypertension.

It turns out that PA is not as rare as once thought.

An eye-catching report in Annals of Internal Medicine this spring of an unexpectedly high prevalence of primary aldosteronism among a diverse cross section of U.S. patients with hypertension has raised issues that could dramatically change the way doctors in America, and elsewhere, assess and manage high blood pressure.

Foremost is the question of whether primary care physicians – the clinicians at the front line for diagnosing and initially treating most patients with hypertension – will absorb and act on this new evidence. For them, aldosteronism doesn’t automatically come to mind when they see high numbers on a BP monitor, and yet this latest research found that up to a third of all 726 patients in the study who were diagnosed with hypertension and with high urinary salt levels had PA.

That translates to a roughly three- to fivefold increase over standard prevalence estimates, and is a ”game changer” for how clinicians should approach hypertension management and PA diagnosis going forward, said John W. Funder, MD, in an editorial accompanying the Annals study.

Long considered relatively uncommon, hypertension driven by an excess of the hormone aldosterone, often because of an adenoma on the adrenal gland, is not the same as conventional “essential” hypertension. The former benefits from early diagnosis because its treatment is completely different – close to half of all PA patients can be treated definitively and quickly with surgical removal of an adenoma from one side of the adrenal gland.

For other PA patients, who have bilateral adrenal hyperplasia that is impossible to resolve surgically, treatment with drugs called mineralocorticoid receptor antagonists (MRAs), such as spironolactone, is needed because they target the hormonal cause of the high BP.

But what usually happens is that a patient with PA is mistakenly diagnosed with essential hypertension, in which the classic approach to treatment is to start with one regular antihypertensive drug, and add on further ones from different drug classes if blood pressure is not adequately controlled. When patients are taking three drugs, without adequate control, they are labeled as having “resistant hypertension.”

But in the case of PA, none of these conventional antihypertensives work, and the process of continuing to monitor and add different drugs wastes time, during which patients deteriorate.

“We need to change the culture of waiting for hypertension to be resistant and have patients riddled with end-organ damage,” due to years of persistently high BP and excess aldosterone “before we look for a secondary cause” like PA, declared Dr. Yang, of Hudson Institute of Medical Research and Monash University in Melbourne, during an interview.

So early diagnosis and prompt treatment of PA is key.

In addition to boosting the public health importance of early PA detection in hypertensive patients, the new up-sized PA prevalence numbers throw a spotlight on primary care physicians (PCPs) as key players who will need to apply the findings to practice on a public health scale.

These novel results create a need for “new guidelines, and a radically revised game plan with the key role of PCPs” emphasized in future management of patients with hypertension, said Dr. Funder, a professor of medicine at Monash University, in a second recent editorial in Hypertension.

“Buy-in by PCPs is essential,” agrees Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville, and a coauthor of the new study.

But he too acknowledges that this presents a major challenge. PCPs and internists, who diagnose a lot of hypertension, are “not used to thinking about aldosterone,” he said in an interview, encapsulating the key problem faced by proponents of earlier and more widespread PA assessment.

This dilemma looms as a “huge public health issue,” Dr. Carey warned.
 

‘We’re a long way from getting’ PCPs to buy in to PA screening

Will PCPs grow more comfortable with screening patients for PA themselves, or might they become more willing to refer hypertensive individuals for assessment at an expert center?

One skeptic is Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg. The finding about high PA prevalence in patients with hypertension “is brand new, [and] the message needs to get to PCPs,” he said. But, “We’re a long way from getting it” to them. “I don’t know how to do that. It will be a tough sell.”

In addition, repositioning MRAs as an earlier option for many hypertensive patients won’t be easy either, because “we’ll never have outcome-trial data for MRAs,” given that they are now generic drugs, he noted.

“No clinical trial data show [MRAs] are first-line drugs,” said Dr. Feldman, who explained that, instead, MRAs are considered “go-to drugs” for patients with treatment-resistant hypertension, a niche therapeutic area. Results from the PATHWAY-2 trial published 5 years ago in Lancet showed “spironolactone was clearly the most effective treatment for the condition,” according to the report authors.

But even among patients with resistant hypertension, screening for PA dramatically lags despite being enshrined in guidelines.

“PCPs should start checking aldosterone-to-renin ratios [a widely used PA screen] in all patients with resistant hypertension or hypertension with hypokalemia, and then refer patients to specialists for testing and management,” said Jordana B. Cohen, MD, a nephrologist and hypertension researcher at the University of Pennsylvania in Philadelphia.

But recent studies of U.S. patient populations with clinical characteristics that meet existing criteria for PA screening showed that just 1%-2% of these individuals underwent an initial PA assessment, she noted, citing reports in the journals Surgery and Hypertension.

“We need to prioritize improving screening in these high-risk patients,” she stressed in an interview.

This illustrates that, in some respects, the new prevalence numbers are beside the point, because PA has been going unscreened and overlooked far too often even in the context of historical, lower prevalence rates, said Dr. Yang.

“The key point is that approximately 1 in 10 people with hypertension, and even more with resistant hypertension, have a form of the disease that is worse than essential hypertension but is routinely missed at present” and is also highly treatable.

“Evidence for the need for increased awareness of PA has been building for 2 decades,” stressed Dr. Yang, who has coauthored several commentaries and reviews that have bemoaned PA’s underappreciated status.
 

Interest in partnering with PCPs on guidance grows

One potential solution is to have endocrinologists and hypertension specialists’ partner with PCPs to come up with diagnostic and management recommendations. Both Dr. Funder and Dr. Carey are opinion leaders regarding the role of aldosterone in hypertension, and both were coauthors of the 2016 Endocrine Society guideline for PA assessment and management published in the Journal of Clinical Endocrinology & Metabolism , with Dr. Funder chairing the writing panel.

Now approaching its fifth year in effect, this guideline is “due for revision,” and “my hope is that we’ll be able to partner with one or more PCP organizations to come up with a version of the guideline targeted to PCPs,” Dr. Carey said.

He voiced interest in working on this with the American College of Physicians, which represents U.S. internal medicine physicians, and the American Academy of Family Physicians.

“We definitely need a partnership and educational efforts to get the word out from these organizations and not from a specialty society,” said Dr. Carey.

Dr. Funder said he has submitted a proposal to the Endocrine Society for a guidelines update he would chair with Dr. Carey’s assistance and with a diverse writing group that includes PCPs. Dr. Carey said that ideally this panel would write and release a revised guideline in 2021.

“Several of us are chomping at the bit to get this done,” he noted.

But participation by the ACP and AAFP remain uncertain as of September 2020. When approached about this, an ACP spokesperson said the organization had no comment. A spokesperson for the AAFP said, “It’s too early to tell if we will partner with any other organizations to develop guidelines specific to excess aldosterone, and how such guidelines might be received by our members.”

Recent history shows little cooperation between ACP, AAFP, and what might be termed the U.S. hypertension “establishment.” For example, when the American College of Cardiology and the American Heart Association released their most recent essential hypertension management guidelines in Hypertension in 2018, it was never adopted by ACP or AAFP.

The latter two organizations continue to endorse a higher BP threshold for diagnosing hypertension, and higher treatment targets set by alternative expert panels to those of the AHA/ACC.
 

Collaboration feasible, although PCPs overworked

Dr. Carey hopes that this episode will not preclude agreement over PA screening.

“I think it is still possible to partner with [the ACP and AAFP],” he observed, adding that he believes high PA prevalence among hypertensive patients and its consequences when unrecognized is “noncontentious.”

But he acknowledges that other, substantial hurdles also exist, notably the “overwhelming workload” that American PCPs already face.

David O’Gurek, MD, a family and community medicine physician at the Lewis Katz School of Medicine of Temple University in Philadelphia, agrees that a revamped approach to PA screening developed cooperatively between PCPs and specialists is an important goal and potentially feasible despite prior disagreements. “There has to be room for collaboration,” he said, but also emphasized the need for developing policies based on a systematic evidence review and a focus on patient-centered outcomes.

“We’re certainly missing patients with PA, but there needs to be greater clarity and standardization about the most appropriate screening approach and cutoff level” for flagging patients who need specialized assessment, Dr. O’Gurek said in an interview.

The current endocrinology literature also shows that experts remain divided on how best to accomplish this.

And some hypertension specialists question whether existing evidence is conclusive enough to warrant revised guidelines.

Dr. Cohen, the nephrologist and hypertension researcher, said that, while the recent prevalence report in Annals of Internal Medicine is “intriguing, hypothesis-generating information that suggests we are missing many cases of hyperaldosteronism in routine care,” she nevertheless believes that “we need additional data to be able to truly understand the breadth and implications of the findings.”

William C. Cushman, MD, a hypertension management specialist at the University of Tennessee Health Science Center in Memphis, agrees.

Changing existing practice guidelines “really needs randomized, controlled trials demonstrating a difference in long-term outcomes, ideally major cardiovascular outcomes,” that result from broader PA screening, he said.

Dr. Carey concurs that more evidence is needed to confirm the Annals report, but is confident this evidence will be in hand by the time a guideline-revision panel meets in 2021.
 

Australian model of PCPs screening for PA could be implemented in United States

An example of what might be possible when PCPs, endocrinologists, and hypertension specialists work together to make PA screening more accessible can be found in Melbourne, at the Endocrine Hypertension Service of Monash Health, in association with the Hudson Institute of Medical Research.

This began operating in July 2016, cofounded by Dr. Yang, whose experiences with her own father made her sensitive to the issue.

The service’s aim is to “address the underdiagnosis of PA, and to offer a streamlined diagnostic service for patients with hypertension,” with an “extensive outreach program” targeted to regional PCPs that, among other messages, encourages them to screen patients for PA when blood pressures exceed 140/90 mm Hg.

During its first 3 years of operation, the service saw 267 patients, with PA diagnosed in 135 and ruled out in 73 patients.

Notably, the proportion of these patients referred from PCPs jumped from 21% of 70 patients during the first year of operation to 47% of 70 patients during year 2, and 52% of 127 patients during the third year, ending in July 2019, said Dr. Yang, who continues to help run the service.

During the first year, a scant 3% of referred patients had recently diagnosed hypertension, but this rose to 14% during the second year, and to 19% during the most recent year with data available.

The median duration of diagnosed hypertension among referred patients fell from 11 years during year 1, to 7 years during year 3.

Service clinicians diagnosed 37 patients with unilateral adenomas, and removed them from 23 patients with four more awaiting surgery and the remaining 10 opting instead for medical management. Another 95 patients went on therapy with a MRA, and during the most recent year studied all patients who began a MRA regimen had a partial or complete clinical response.

Dr. Carey said the “creative program represents a model for implementation in U.S. practice.

Dr. Funder, Dr. Carey, Dr. Feldman, Dr. Yang, Dr. Cohen, and Dr. O’Gurek had no relevant disclosures. Dr. Cushman has been a consultant to Novartis, received personal fees from Sanofi, and research funding from Eli Lilly.

[email protected]

Patients with type 2 or type 1 diabetes who stay in a blood glucose range of 70-180 mg/dL at least 70% of the time have the lowest rates of major adverse coronary events, severe hypoglycemic episodes, and microvascular events, according to a post hoc analysis of data collected from 5,774 patients with type 2 diabetes.

Data collected by the DEVOTE trial showed that every additional 10% of the time that a patient with type 2 diabetes (T2D) spent in their target range for blood glucose linked with a significant 6% reduced rate for developing a major adverse cardiovascular event (MACE), Richard M. Bergenstal, MD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

For every 10% increase in time in range (TIR), patients showed an average 10% drop in their incidence of severe hypoglycemic episodes.
 

Increasing evidence from post hoc analyses

These findings confirmed a prior post hoc analysis of data collected in the DCCT trial (NCT00360815), which were published in the New England Journal of Medicine, although those results showed significant relationships between increased TIR and decreased rates of retinopathy and microalbuminuria. For every 10% drop in TIR, retinopathy rose by 64% and microalbuminuria increased by 40%, according to a post hoc analysis of the DCCT data that Dr. Bergenstal helped run and was published in Diabetes Care.

“It’s becoming clear that time in range is an important metric for diabetes management, and our new findings and those previously reported with the DCCT data make it look like time in range is becoming a good marker for clinical outcomes as well,” said Dr. Bergenstal, an endocrinologist at the Park Nicollet Clinic in Minneapolis.

“It’s a new concept, getting time-in-range data,” said Dr. Bergenstal, who was a coauthor of recommendations from Diabetes Care that were made in 2019 by an expert panel organized by the Advanced Technologies & Treatments for Diabetes Congress. “We think this will be a good marker to keep glycemia in a safe range, and the results look positive.” Patients who stay in the blood glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) at least 70% of the time generally have an hemoglobin A_1c of about 7%, which is what makes it a good target for patients and clinicians to focus on. Patients with a 50% TIR rate generally have an HbA_1c of about 8%.

But a TIR assessment can be more informative than HbA_1c, said the 2019 recommendations document. It called TIR assessments “appropriate and useful as clinical targets and outcome measurements that complement A1c for a wide range of people with diabetes.”
 

Data mining from DEVOTE

The analysis run by Dr. Bergenstal and his associates used data from 5,774 of the 7,637 patients enrolled in the DEVOTE trial, for whom adequate longitudinal blood glucose data were available to derive and track TIR. DEVOTE had the primary aim of comparing two different types of insulin in patients with T2D, according to its explanation in the New England Journal of Medicine. The DEVOTE patients did not undergo routine continuous blood glucose monitoring, so derivation of TIR was the only option with the dataset, Dr. Bergenstal said. “We’re trying to get continuous blood monitoring into T2D trials,” he said.

The post hoc analysis showed that, during the study’s follow-up of just under 2 years, patients who maintained a derived TIR of 70%-100% had about a 6% MACE rate, which peaked at nearly twice that in patients whose TIR was 30% or less. The analysis showed a roughly positive linear relationship between TIR and MACE rates across the range of TIR values. In an adjusted analysis, patients with at least a 70% TIR had a significant 31% lower rate of MACE events, compared with patients whose TIR was 50% or less.

A second analysis that looked for the association between TIR and incidence of hypoglycemic episodes showed a somewhat similar positive relationship, with incidence rates of severe hypoglycemia episodes of about 4%-5% among patients with a TIR of 70% or greater, and a rate of about 7% in patients with a TIR of 30% or less, spiking to 14% among patients with a TIR of 10% or less. In an adjusted analysis, patients with a TIR of at least 70% had a significant 46% lower rate of severe hypoglycemic events, compared with patients whose TIR was 50% or less. This finding belies a common misconception that the tighter glycemic control that produces a higher TIR will lead to increased episodes of severe hypoglycemia, Dr. Bergenstal noted.

He also reported less extensive data on microvascular events. In an adjusted analysis, patients with a TIR of at least 70% had a significant 40% cut in these events compared with patients with 50% or less TIR.

DEVOTE was funded by Novo Nordisk. Dr. Bergenstal has had financial relationships with Novo Nordisk and several other companies.

[email protected]

SOURCE: Bergenstal R et al. EASD 2020, abstract 159.

Patients with type 2 or type 1 diabetes who stay in a blood glucose range of 70-180 mg/dL at least 70% of the time have the lowest rates of major adverse coronary events, severe hypoglycemic episodes, and microvascular events, according to a post hoc analysis of data collected from 5,774 patients with type 2 diabetes.

Data collected by the DEVOTE trial showed that every additional 10% of the time that a patient with type 2 diabetes (T2D) spent in their target range for blood glucose linked with a significant 6% reduced rate for developing a major adverse cardiovascular event (MACE), Richard M. Bergenstal, MD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

For every 10% increase in time in range (TIR), patients showed an average 10% drop in their incidence of severe hypoglycemic episodes.
 

Increasing evidence from post hoc analyses

These findings confirmed a prior post hoc analysis of data collected in the DCCT trial (NCT00360815), which were published in the New England Journal of Medicine, although those results showed significant relationships between increased TIR and decreased rates of retinopathy and microalbuminuria. For every 10% drop in TIR, retinopathy rose by 64% and microalbuminuria increased by 40%, according to a post hoc analysis of the DCCT data that Dr. Bergenstal helped run and was published in Diabetes Care.

“It’s becoming clear that time in range is an important metric for diabetes management, and our new findings and those previously reported with the DCCT data make it look like time in range is becoming a good marker for clinical outcomes as well,” said Dr. Bergenstal, an endocrinologist at the Park Nicollet Clinic in Minneapolis.

“It’s a new concept, getting time-in-range data,” said Dr. Bergenstal, who was a coauthor of recommendations from Diabetes Care that were made in 2019 by an expert panel organized by the Advanced Technologies & Treatments for Diabetes Congress. “We think this will be a good marker to keep glycemia in a safe range, and the results look positive.” Patients who stay in the blood glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) at least 70% of the time generally have an hemoglobin A_1c of about 7%, which is what makes it a good target for patients and clinicians to focus on. Patients with a 50% TIR rate generally have an HbA_1c of about 8%.

But a TIR assessment can be more informative than HbA_1c, said the 2019 recommendations document. It called TIR assessments “appropriate and useful as clinical targets and outcome measurements that complement A1c for a wide range of people with diabetes.”
 

Data mining from DEVOTE

The analysis run by Dr. Bergenstal and his associates used data from 5,774 of the 7,637 patients enrolled in the DEVOTE trial, for whom adequate longitudinal blood glucose data were available to derive and track TIR. DEVOTE had the primary aim of comparing two different types of insulin in patients with T2D, according to its explanation in the New England Journal of Medicine. The DEVOTE patients did not undergo routine continuous blood glucose monitoring, so derivation of TIR was the only option with the dataset, Dr. Bergenstal said. “We’re trying to get continuous blood monitoring into T2D trials,” he said.

The post hoc analysis showed that, during the study’s follow-up of just under 2 years, patients who maintained a derived TIR of 70%-100% had about a 6% MACE rate, which peaked at nearly twice that in patients whose TIR was 30% or less. The analysis showed a roughly positive linear relationship between TIR and MACE rates across the range of TIR values. In an adjusted analysis, patients with at least a 70% TIR had a significant 31% lower rate of MACE events, compared with patients whose TIR was 50% or less.

A second analysis that looked for the association between TIR and incidence of hypoglycemic episodes showed a somewhat similar positive relationship, with incidence rates of severe hypoglycemia episodes of about 4%-5% among patients with a TIR of 70% or greater, and a rate of about 7% in patients with a TIR of 30% or less, spiking to 14% among patients with a TIR of 10% or less. In an adjusted analysis, patients with a TIR of at least 70% had a significant 46% lower rate of severe hypoglycemic events, compared with patients whose TIR was 50% or less. This finding belies a common misconception that the tighter glycemic control that produces a higher TIR will lead to increased episodes of severe hypoglycemia, Dr. Bergenstal noted.

He also reported less extensive data on microvascular events. In an adjusted analysis, patients with a TIR of at least 70% had a significant 40% cut in these events compared with patients with 50% or less TIR.

DEVOTE was funded by Novo Nordisk. Dr. Bergenstal has had financial relationships with Novo Nordisk and several other companies.

[email protected]

SOURCE: Bergenstal R et al. EASD 2020, abstract 159.

Patients with type 2 or type 1 diabetes who stay in a blood glucose range of 70-180 mg/dL at least 70% of the time have the lowest rates of major adverse coronary events, severe hypoglycemic episodes, and microvascular events, according to a post hoc analysis of data collected from 5,774 patients with type 2 diabetes.

Data collected by the DEVOTE trial showed that every additional 10% of the time that a patient with type 2 diabetes (T2D) spent in their target range for blood glucose linked with a significant 6% reduced rate for developing a major adverse cardiovascular event (MACE), Richard M. Bergenstal, MD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

For every 10% increase in time in range (TIR), patients showed an average 10% drop in their incidence of severe hypoglycemic episodes.
 

Increasing evidence from post hoc analyses

These findings confirmed a prior post hoc analysis of data collected in the DCCT trial (NCT00360815), which were published in the New England Journal of Medicine, although those results showed significant relationships between increased TIR and decreased rates of retinopathy and microalbuminuria. For every 10% drop in TIR, retinopathy rose by 64% and microalbuminuria increased by 40%, according to a post hoc analysis of the DCCT data that Dr. Bergenstal helped run and was published in Diabetes Care.

“It’s becoming clear that time in range is an important metric for diabetes management, and our new findings and those previously reported with the DCCT data make it look like time in range is becoming a good marker for clinical outcomes as well,” said Dr. Bergenstal, an endocrinologist at the Park Nicollet Clinic in Minneapolis.

“It’s a new concept, getting time-in-range data,” said Dr. Bergenstal, who was a coauthor of recommendations from Diabetes Care that were made in 2019 by an expert panel organized by the Advanced Technologies & Treatments for Diabetes Congress. “We think this will be a good marker to keep glycemia in a safe range, and the results look positive.” Patients who stay in the blood glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) at least 70% of the time generally have an hemoglobin A_1c of about 7%, which is what makes it a good target for patients and clinicians to focus on. Patients with a 50% TIR rate generally have an HbA_1c of about 8%.

But a TIR assessment can be more informative than HbA_1c, said the 2019 recommendations document. It called TIR assessments “appropriate and useful as clinical targets and outcome measurements that complement A1c for a wide range of people with diabetes.”
 

Data mining from DEVOTE

The analysis run by Dr. Bergenstal and his associates used data from 5,774 of the 7,637 patients enrolled in the DEVOTE trial, for whom adequate longitudinal blood glucose data were available to derive and track TIR. DEVOTE had the primary aim of comparing two different types of insulin in patients with T2D, according to its explanation in the New England Journal of Medicine. The DEVOTE patients did not undergo routine continuous blood glucose monitoring, so derivation of TIR was the only option with the dataset, Dr. Bergenstal said. “We’re trying to get continuous blood monitoring into T2D trials,” he said.

The post hoc analysis showed that, during the study’s follow-up of just under 2 years, patients who maintained a derived TIR of 70%-100% had about a 6% MACE rate, which peaked at nearly twice that in patients whose TIR was 30% or less. The analysis showed a roughly positive linear relationship between TIR and MACE rates across the range of TIR values. In an adjusted analysis, patients with at least a 70% TIR had a significant 31% lower rate of MACE events, compared with patients whose TIR was 50% or less.

A second analysis that looked for the association between TIR and incidence of hypoglycemic episodes showed a somewhat similar positive relationship, with incidence rates of severe hypoglycemia episodes of about 4%-5% among patients with a TIR of 70% or greater, and a rate of about 7% in patients with a TIR of 30% or less, spiking to 14% among patients with a TIR of 10% or less. In an adjusted analysis, patients with a TIR of at least 70% had a significant 46% lower rate of severe hypoglycemic events, compared with patients whose TIR was 50% or less. This finding belies a common misconception that the tighter glycemic control that produces a higher TIR will lead to increased episodes of severe hypoglycemia, Dr. Bergenstal noted.

He also reported less extensive data on microvascular events. In an adjusted analysis, patients with a TIR of at least 70% had a significant 40% cut in these events compared with patients with 50% or less TIR.

DEVOTE was funded by Novo Nordisk. Dr. Bergenstal has had financial relationships with Novo Nordisk and several other companies.

[email protected]

SOURCE: Bergenstal R et al. EASD 2020, abstract 159.

Type 2 diabetes patients could lower their risk for death from any cause by up to a third by exercising at a moderate to high level or by cycling, according to data from two studies reported at the virtual annual meeting of the European Association for the Study of Diabetes.

Yun-Ju Lai, MD, and colleagues from the Puli branch of Taichung Veterans General Hospital in Nantou, Taiwan, found that persons with type 2 diabetes who exercised at moderate to high intensity had a 25%-32% decreased risk for death, compared with those who did not exercise.

In a separate study, Mathias Ried-Larsen, MSc, PhD, group leader at the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and associates found that cycling was associated with a 25%-31% decreased risk for all-cause death compared to no cycling, and that cycling also reduced cardiovascular mortality.
 

Results fit with ADA recommendations

“There is really nothing surprising about these results as others have shown that regular participation in physical activity lowers both overall mortality rates and morbidity,” commented Sheri Colberg-Ochs, PhD, professor emerita in exercise science at Old Dominion University in Norfolk, Va., in an interview.

“Regular exercise participation lowers the risk of mortality in almost all populations with many different health conditions. It is not specific to people with type 2 diabetes,” Dr. Colberg-Ochs said. “These data add further support to the ADA [American Diabetes Association] recommendations by again suggesting that being more active leads to many health benefits for people with type 2 diabetes.”

Dr. Colberg-Ochs, who was not involved in either study, is recognized by the ADA as an Outstanding Educator in Diabetes. She was also involved in writing the ADA’s position statement on physical activity/exercise in diabetes, which advocate that adults with type 2 diabetes should reduce sedentary time and undertake both aerobic and resistance exercise training to help optimize their glycemic and general health outcomes.
 

Asian population understudied

In an interview Dr. Lai acknowledged that epidemiologic studies had shown that exercise reduced the risk of cardiovascular events and mortality in subjects with type 2 diabetes. “However, the dose of exercise capacity for reducing mortality risk in people with type 2 diabetes was not yet well investigated, especially in the Asian population.”

Dr. Lai and colleagues analyzed data on 4,859 subjects drawn from two Taiwanese databases – the National Health Interview Survey and the National Health Insurance research database – to study what effect exercise “capacity” had on the risk for death in those with type 2 diabetes.

“Information about physical activity during leisure time was collected by asking the questions: ‘How often do you exercise every week? What kind of exercise do you do? How long do you do the exercise?’, Dr. Lai said. “We included nearly all kinds of exercise in the analysis, such as jogging, swimming, walking, dancing, riding, and so on.”

Each exercise had an activity intensity code expressed as kilocalories per minute. This was used to determine the exercise “capacity” by multiplying it by how frequently the exercise was performed per week and for how long each time.

“I don’t think ‘capacity’ is the right word to use here. The equation they used describes their exercise ‘volume,’ not their capacity. Self-reported exercise is notoriously inaccurate,” Dr. Colberg-Ochs observed. Furthermore, “just asking people how much they exercise and at what intensity [without using a validated exercise questionnaire] gives questionable results.”

The study’s findings, however, were clear: Those who exercised at a higher level had a significantly decreased risk for all-cause mortality than did those with no exercise habits. The hazard ratio for death by any cause was 0.75 for those who undertook a moderate level of exercise, burning 0-800 kcal per week. Exercising at a higher level burned more than 800 kcal had a HR of 0.68. A significant (P < .01) trend in favor of more exercise was noted.
 

Cycling reduces all-cause and cardiovascular mortality

In their prospective cohort study, Dr. Ried-Larsen and associates took a more specific look at the effects of exercise on mortality in diabetes by studying a single exercise: cycling. They sampled data on more than 5,000 people collected as part of the European Prospective Investigation into Cancer and Nutrition study. First, they identified participants with diabetes – although they couldn’t distinguish type 1 from type 2 forms because this was self-reported or obtained from registries. They then identified those who reported cycling at their baseline assessment and those who reported a change in cycling habits at their second examination around 5 years later.

At baseline, 38% of participants reported that they cycled every week. The mean age was 56 years, diabetes duration was 8 years, one-fifth were smokers, and the average body mass index was 29 kg/m².

Participants who reported cycling up to 1 hour every week at baseline had a 25% reduction in all-cause mortality, compared with those who did not cycle. The biggest reduction (31%) in all-cause mortality was seen for cycling 2.5-5 hours a week; cycling for 1-2.5 hours, and for more than 5 hours, yielded 23% and 24% risk reductions, respectively.

A reverse J–shaped relationship between cycling duration and reduction in all-cause mortality was seen, Dr. Ried-Larsen noted during a live oral session at the virtual meeting. “The maximum benefit [was at] around 5 hours per week, and the benefits persisted until around 9 hours per week.” Adjustment for the prevalence of stroke, MI, cancer, hyperlipidemia, hypertension, and central obesity did not alter the findings.

“The direction of the association was the same for cardiovascular mortality as all-cause mortality, although a bit weaker, with the maximum benefit being around 4 hours per week, and that persisted up until around 8 hours per week,” Dr. Ried-Larsen said.

The benefits of cycling on all-cause and cardiovascular mortality were lost, however, if those who cycled at baseline stopped by the second examination. Those who did not cycle at the first but did at the second examination got a benefit on both, as did those who continued cycling.

“Cycling is among one of the preferred activities for diabetes patients, so it actually may help them to achieve the recommend level of physical activity,” Dr. Ried-Larsen said.
 

Tailored exercise program important

Advice for exercise “should be tailored to the individual and based on starting fitness levels and activity levels,” Dr. Colberg-Ochs recommended.

“Those who are the most sedentary and the least fit have the most to gain from doing any activity. They should be advised to start out slowly and progress slowly with both aerobic activities and some resistance training,” Dr. Colberg-Ochs said.

She added: “In addition, individuals over 40 should engage in regular balance training, and all individuals should do some flexibility exercises.”

The studies received no commercial funding and all those mentioned in this article had no conflicts of interest to disclose.

SOURCE: Lai Y-J et al. EASD 2020, Poster presentation 267; Ried-Larsen M et al. EASD 2020, Oral presentation 194.

Type 2 diabetes patients could lower their risk for death from any cause by up to a third by exercising at a moderate to high level or by cycling, according to data from two studies reported at the virtual annual meeting of the European Association for the Study of Diabetes.

Yun-Ju Lai, MD, and colleagues from the Puli branch of Taichung Veterans General Hospital in Nantou, Taiwan, found that persons with type 2 diabetes who exercised at moderate to high intensity had a 25%-32% decreased risk for death, compared with those who did not exercise.

In a separate study, Mathias Ried-Larsen, MSc, PhD, group leader at the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and associates found that cycling was associated with a 25%-31% decreased risk for all-cause death compared to no cycling, and that cycling also reduced cardiovascular mortality.
 

Results fit with ADA recommendations

“There is really nothing surprising about these results as others have shown that regular participation in physical activity lowers both overall mortality rates and morbidity,” commented Sheri Colberg-Ochs, PhD, professor emerita in exercise science at Old Dominion University in Norfolk, Va., in an interview.

“Regular exercise participation lowers the risk of mortality in almost all populations with many different health conditions. It is not specific to people with type 2 diabetes,” Dr. Colberg-Ochs said. “These data add further support to the ADA [American Diabetes Association] recommendations by again suggesting that being more active leads to many health benefits for people with type 2 diabetes.”

Dr. Colberg-Ochs, who was not involved in either study, is recognized by the ADA as an Outstanding Educator in Diabetes. She was also involved in writing the ADA’s position statement on physical activity/exercise in diabetes, which advocate that adults with type 2 diabetes should reduce sedentary time and undertake both aerobic and resistance exercise training to help optimize their glycemic and general health outcomes.
 

Asian population understudied

In an interview Dr. Lai acknowledged that epidemiologic studies had shown that exercise reduced the risk of cardiovascular events and mortality in subjects with type 2 diabetes. “However, the dose of exercise capacity for reducing mortality risk in people with type 2 diabetes was not yet well investigated, especially in the Asian population.”

Dr. Lai and colleagues analyzed data on 4,859 subjects drawn from two Taiwanese databases – the National Health Interview Survey and the National Health Insurance research database – to study what effect exercise “capacity” had on the risk for death in those with type 2 diabetes.

“Information about physical activity during leisure time was collected by asking the questions: ‘How often do you exercise every week? What kind of exercise do you do? How long do you do the exercise?’, Dr. Lai said. “We included nearly all kinds of exercise in the analysis, such as jogging, swimming, walking, dancing, riding, and so on.”

Each exercise had an activity intensity code expressed as kilocalories per minute. This was used to determine the exercise “capacity” by multiplying it by how frequently the exercise was performed per week and for how long each time.

“I don’t think ‘capacity’ is the right word to use here. The equation they used describes their exercise ‘volume,’ not their capacity. Self-reported exercise is notoriously inaccurate,” Dr. Colberg-Ochs observed. Furthermore, “just asking people how much they exercise and at what intensity [without using a validated exercise questionnaire] gives questionable results.”

The study’s findings, however, were clear: Those who exercised at a higher level had a significantly decreased risk for all-cause mortality than did those with no exercise habits. The hazard ratio for death by any cause was 0.75 for those who undertook a moderate level of exercise, burning 0-800 kcal per week. Exercising at a higher level burned more than 800 kcal had a HR of 0.68. A significant (P < .01) trend in favor of more exercise was noted.
 

Cycling reduces all-cause and cardiovascular mortality

In their prospective cohort study, Dr. Ried-Larsen and associates took a more specific look at the effects of exercise on mortality in diabetes by studying a single exercise: cycling. They sampled data on more than 5,000 people collected as part of the European Prospective Investigation into Cancer and Nutrition study. First, they identified participants with diabetes – although they couldn’t distinguish type 1 from type 2 forms because this was self-reported or obtained from registries. They then identified those who reported cycling at their baseline assessment and those who reported a change in cycling habits at their second examination around 5 years later.

At baseline, 38% of participants reported that they cycled every week. The mean age was 56 years, diabetes duration was 8 years, one-fifth were smokers, and the average body mass index was 29 kg/m².

Participants who reported cycling up to 1 hour every week at baseline had a 25% reduction in all-cause mortality, compared with those who did not cycle. The biggest reduction (31%) in all-cause mortality was seen for cycling 2.5-5 hours a week; cycling for 1-2.5 hours, and for more than 5 hours, yielded 23% and 24% risk reductions, respectively.

A reverse J–shaped relationship between cycling duration and reduction in all-cause mortality was seen, Dr. Ried-Larsen noted during a live oral session at the virtual meeting. “The maximum benefit [was at] around 5 hours per week, and the benefits persisted until around 9 hours per week.” Adjustment for the prevalence of stroke, MI, cancer, hyperlipidemia, hypertension, and central obesity did not alter the findings.

“The direction of the association was the same for cardiovascular mortality as all-cause mortality, although a bit weaker, with the maximum benefit being around 4 hours per week, and that persisted up until around 8 hours per week,” Dr. Ried-Larsen said.

The benefits of cycling on all-cause and cardiovascular mortality were lost, however, if those who cycled at baseline stopped by the second examination. Those who did not cycle at the first but did at the second examination got a benefit on both, as did those who continued cycling.

“Cycling is among one of the preferred activities for diabetes patients, so it actually may help them to achieve the recommend level of physical activity,” Dr. Ried-Larsen said.
 

Tailored exercise program important

Advice for exercise “should be tailored to the individual and based on starting fitness levels and activity levels,” Dr. Colberg-Ochs recommended.

“Those who are the most sedentary and the least fit have the most to gain from doing any activity. They should be advised to start out slowly and progress slowly with both aerobic activities and some resistance training,” Dr. Colberg-Ochs said.

She added: “In addition, individuals over 40 should engage in regular balance training, and all individuals should do some flexibility exercises.”

The studies received no commercial funding and all those mentioned in this article had no conflicts of interest to disclose.

SOURCE: Lai Y-J et al. EASD 2020, Poster presentation 267; Ried-Larsen M et al. EASD 2020, Oral presentation 194.

Type 2 diabetes patients could lower their risk for death from any cause by up to a third by exercising at a moderate to high level or by cycling, according to data from two studies reported at the virtual annual meeting of the European Association for the Study of Diabetes.

Yun-Ju Lai, MD, and colleagues from the Puli branch of Taichung Veterans General Hospital in Nantou, Taiwan, found that persons with type 2 diabetes who exercised at moderate to high intensity had a 25%-32% decreased risk for death, compared with those who did not exercise.

In a separate study, Mathias Ried-Larsen, MSc, PhD, group leader at the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and associates found that cycling was associated with a 25%-31% decreased risk for all-cause death compared to no cycling, and that cycling also reduced cardiovascular mortality.
 

Results fit with ADA recommendations

“There is really nothing surprising about these results as others have shown that regular participation in physical activity lowers both overall mortality rates and morbidity,” commented Sheri Colberg-Ochs, PhD, professor emerita in exercise science at Old Dominion University in Norfolk, Va., in an interview.

“Regular exercise participation lowers the risk of mortality in almost all populations with many different health conditions. It is not specific to people with type 2 diabetes,” Dr. Colberg-Ochs said. “These data add further support to the ADA [American Diabetes Association] recommendations by again suggesting that being more active leads to many health benefits for people with type 2 diabetes.”

Dr. Colberg-Ochs, who was not involved in either study, is recognized by the ADA as an Outstanding Educator in Diabetes. She was also involved in writing the ADA’s position statement on physical activity/exercise in diabetes, which advocate that adults with type 2 diabetes should reduce sedentary time and undertake both aerobic and resistance exercise training to help optimize their glycemic and general health outcomes.
 

Asian population understudied

In an interview Dr. Lai acknowledged that epidemiologic studies had shown that exercise reduced the risk of cardiovascular events and mortality in subjects with type 2 diabetes. “However, the dose of exercise capacity for reducing mortality risk in people with type 2 diabetes was not yet well investigated, especially in the Asian population.”

Dr. Lai and colleagues analyzed data on 4,859 subjects drawn from two Taiwanese databases – the National Health Interview Survey and the National Health Insurance research database – to study what effect exercise “capacity” had on the risk for death in those with type 2 diabetes.

“Information about physical activity during leisure time was collected by asking the questions: ‘How often do you exercise every week? What kind of exercise do you do? How long do you do the exercise?’, Dr. Lai said. “We included nearly all kinds of exercise in the analysis, such as jogging, swimming, walking, dancing, riding, and so on.”

Each exercise had an activity intensity code expressed as kilocalories per minute. This was used to determine the exercise “capacity” by multiplying it by how frequently the exercise was performed per week and for how long each time.

“I don’t think ‘capacity’ is the right word to use here. The equation they used describes their exercise ‘volume,’ not their capacity. Self-reported exercise is notoriously inaccurate,” Dr. Colberg-Ochs observed. Furthermore, “just asking people how much they exercise and at what intensity [without using a validated exercise questionnaire] gives questionable results.”

The study’s findings, however, were clear: Those who exercised at a higher level had a significantly decreased risk for all-cause mortality than did those with no exercise habits. The hazard ratio for death by any cause was 0.75 for those who undertook a moderate level of exercise, burning 0-800 kcal per week. Exercising at a higher level burned more than 800 kcal had a HR of 0.68. A significant (P < .01) trend in favor of more exercise was noted.
 

Cycling reduces all-cause and cardiovascular mortality

In their prospective cohort study, Dr. Ried-Larsen and associates took a more specific look at the effects of exercise on mortality in diabetes by studying a single exercise: cycling. They sampled data on more than 5,000 people collected as part of the European Prospective Investigation into Cancer and Nutrition study. First, they identified participants with diabetes – although they couldn’t distinguish type 1 from type 2 forms because this was self-reported or obtained from registries. They then identified those who reported cycling at their baseline assessment and those who reported a change in cycling habits at their second examination around 5 years later.

At baseline, 38% of participants reported that they cycled every week. The mean age was 56 years, diabetes duration was 8 years, one-fifth were smokers, and the average body mass index was 29 kg/m².

Participants who reported cycling up to 1 hour every week at baseline had a 25% reduction in all-cause mortality, compared with those who did not cycle. The biggest reduction (31%) in all-cause mortality was seen for cycling 2.5-5 hours a week; cycling for 1-2.5 hours, and for more than 5 hours, yielded 23% and 24% risk reductions, respectively.

A reverse J–shaped relationship between cycling duration and reduction in all-cause mortality was seen, Dr. Ried-Larsen noted during a live oral session at the virtual meeting. “The maximum benefit [was at] around 5 hours per week, and the benefits persisted until around 9 hours per week.” Adjustment for the prevalence of stroke, MI, cancer, hyperlipidemia, hypertension, and central obesity did not alter the findings.

“The direction of the association was the same for cardiovascular mortality as all-cause mortality, although a bit weaker, with the maximum benefit being around 4 hours per week, and that persisted up until around 8 hours per week,” Dr. Ried-Larsen said.

The benefits of cycling on all-cause and cardiovascular mortality were lost, however, if those who cycled at baseline stopped by the second examination. Those who did not cycle at the first but did at the second examination got a benefit on both, as did those who continued cycling.

“Cycling is among one of the preferred activities for diabetes patients, so it actually may help them to achieve the recommend level of physical activity,” Dr. Ried-Larsen said.
 

Tailored exercise program important

Advice for exercise “should be tailored to the individual and based on starting fitness levels and activity levels,” Dr. Colberg-Ochs recommended.

“Those who are the most sedentary and the least fit have the most to gain from doing any activity. They should be advised to start out slowly and progress slowly with both aerobic activities and some resistance training,” Dr. Colberg-Ochs said.

She added: “In addition, individuals over 40 should engage in regular balance training, and all individuals should do some flexibility exercises.”

The studies received no commercial funding and all those mentioned in this article had no conflicts of interest to disclose.

SOURCE: Lai Y-J et al. EASD 2020, Poster presentation 267; Ried-Larsen M et al. EASD 2020, Oral presentation 194.

The dramatically positive safety and efficacy results from the DAPA-CKD trial, which showed that treatment with the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin significantly cut both chronic kidney disease progression and all-cause death in patients with or without type 2 diabetes, were also notable for broadening the population of patients eligible for this treatment to those in the upper range of stage 4 CKD.

Courtesy European Society of Cardiology

Of the 4,304 CKD patients enrolled in DAPA-CKD, 624 (14%) had an estimated glomerular filtration rate (eGFR) of 25-29 mL/min per 1.73m², an unprecedented population to receive a drug from the SGLT2 inhibitor class in a reported study. The results provided definitive evidence for efficacy and safety in this range of renal function, said Hiddo J.L. Heerspink, Ph.D., at the virtual annual meeting of the European Association for the Study of Diabetes.

Until now, the widely accepted lowest level for starting an SGLT2 inhibitor in routine practice has been an eGFR as low as 30 mL/min per 1.73 m².
 

Using SGLT2 inhibitors when eGFR is as low as 25

“It’s time to reduce the eGFR level for initiating an SGLT2 inhibitor to as low as 25,” said Dr. Heerspink, a professor of clinical pharmacology at the University of Groningen (the Netherlands).

While conceding that this is primarily a decision to be made by guideline writers and regulatory bodies, he declared what he believed was established by the DAPA-CKD findings: “We’ve shown that dapagliflozin can be safely used in these patients. It is effective across the spectrum of kidney function.”

Other experts not associated with the study agreed.

Sara Freeman/MDedge News

The trial researchers were “brave” to enroll patients with eGFRs as low as 25 mL/min per 1.73 m², and “we urgently need these agents in patients with an eGFR this low,” commented Chantal Mathieu, MD, an endocrinologist and professor of medicine at Catholic University in Leuven, Belgium, and designated discussant for the report. Overall, she called the findings “spectacular,” a “landmark trial,” and a “winner.”

The study also set an new, lower floor for the level of albuminuria that can be usefully treated with dapagliflozin (Farxiga) by enrolling patients with a urinary albumin-to-creatinine ratio as low as 200 mg/g; the previous lower limit had been 300 mg/g, noted Dr. Mathieu. The new findings pose challenges to guideline writers, regulators who approve drug labels, and payers to a quickly make changes that will bring dapagliflozin to a wider number of patients with CKD.

Once the full DAPA-CKD results are reported, “it will change practice, and push the eGFR needle down” to as low as 25. It will also lower the albuminuria threshold for using dapagliflozin or other drugs in the class, commented David Z.I. Cherney, MD, a nephrologist at the University of Toronto. “It’s just one study,” he admitted, but the consistent renal benefits seen across several studies involving all four drugs in the SGLT2 inhibitor class will help hasten this change in identifying treatable patients, as well as expand the drug class to patients with CKD but no type 2 diabetes (T2D).

“I don’t think we’ve ever had stronger evidence” for drugs that can benefit both heart and renal function, plus the drug class is “very safe, and really easy to start” and maintain in patients, Dr. Cherney said in an interview. “It’s wonderful for these patients that we now have something new for treatment,” a drug with a “very favorable benefit-to-risk ratio.”
 

Results show many dapagliflozin benefits

While this broadening of the range of patients proven to tolerate and benefit from an SGLT2 inhibitor was an important consequence of DAPA-CKD, the study’s primary finding – that dapagliflozin was as safe and effective for slowing CKD progression in patients regardless of whether they also had T2D – will have an even bigger impact on expanding the target patient population. Showing efficacy in patients with CKD but without a T2D etiology, the status of about a third of the enrolled 4,304 patients, makes this treatment an option for “millions” of additional patients worldwide, said Dr. Heerspink. “These are the most common patients nephrologists see.” A major challenge now will be to do a better job finding patients with CKD who could benefit from dapagliflozin.

DAPA-CKD enrolled CKD patients based primarily on prespecified albuminuria and eGFR levels at more than 300 centers in 34 countries, including the United States. Virtually all patients, 97%, were on the only treatment now available with proven efficacy for slowing CKD, either an ACE inhibitor or an angiotensin receptor blocker. The small number of patients not on one of these drugs was because of poor tolerance.

The study’s primary endpoint was the combined rate of cardiovascular death, renal death, end-stage renal disease, or a drop in eGFR of at least 50% from baseline. This occurred in 14.5% of patients who received placebo and in 9.2% of those who received dapagliflozin during a median follow-up of 2.4 years, a highly significant 39% relative risk reduction. Concurrently with the report at the virtual meeting the results also appeared online in the New England Journal of Medicine. This 5.3% cut in the absolute rate of the combined, primary adverse outcome converted into a number needed to treat of 19 to prevent 1 event during 2.4 years, a “much lower” number needed to treat than reported for renin-angiotensin system inhibitors in these types of patients, Dr. Heerspink said.

Notable positive secondary outcomes included a significant 31% relative cut (a 2% absolute decline) in all-cause mortality, “a major highlight” of the findings, Dr. Heerspink said. Dapagliflozin treatment also linked with a significant 29% relative cut in the incidence of cardiovascular death or hospitalization for heart failure.

“Cardiovascular disease is the most common cause of death in patients with CKD,” explained David C. Wheeler, MD, a coinvestigator on the study and professor of kidney medicine at University College London. “The heart and kidney are intertwined. This is about cardiorenal disease.”

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Heerspink has been a consultant to and received research funding from AstraZeneca. He has also received personal fees from Mundipharma and Novo Nordisk, and he has also served as consultant to several other companies with the honoraria being paid to his institution. Dr. Mathieu has had relationships with AstraZeneca and several other companies. Dr. Cherney has been a consultant to and has received research funding from AstraZeneca and several other companies. Dr. Wheeler has received personal fees from AstraZeneca and from several other companies.

[email protected]

SOURCE: Heerspink HJL et al. EASD 2020 and N Engl J Med. 2020 Sep 24. doi: 10.1056/NEJMoa2024816.

The dramatically positive safety and efficacy results from the DAPA-CKD trial, which showed that treatment with the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin significantly cut both chronic kidney disease progression and all-cause death in patients with or without type 2 diabetes, were also notable for broadening the population of patients eligible for this treatment to those in the upper range of stage 4 CKD.

Courtesy European Society of Cardiology

Of the 4,304 CKD patients enrolled in DAPA-CKD, 624 (14%) had an estimated glomerular filtration rate (eGFR) of 25-29 mL/min per 1.73m², an unprecedented population to receive a drug from the SGLT2 inhibitor class in a reported study. The results provided definitive evidence for efficacy and safety in this range of renal function, said Hiddo J.L. Heerspink, Ph.D., at the virtual annual meeting of the European Association for the Study of Diabetes.

Until now, the widely accepted lowest level for starting an SGLT2 inhibitor in routine practice has been an eGFR as low as 30 mL/min per 1.73 m².
 

Using SGLT2 inhibitors when eGFR is as low as 25

“It’s time to reduce the eGFR level for initiating an SGLT2 inhibitor to as low as 25,” said Dr. Heerspink, a professor of clinical pharmacology at the University of Groningen (the Netherlands).

While conceding that this is primarily a decision to be made by guideline writers and regulatory bodies, he declared what he believed was established by the DAPA-CKD findings: “We’ve shown that dapagliflozin can be safely used in these patients. It is effective across the spectrum of kidney function.”

Other experts not associated with the study agreed.

Sara Freeman/MDedge News

The trial researchers were “brave” to enroll patients with eGFRs as low as 25 mL/min per 1.73 m², and “we urgently need these agents in patients with an eGFR this low,” commented Chantal Mathieu, MD, an endocrinologist and professor of medicine at Catholic University in Leuven, Belgium, and designated discussant for the report. Overall, she called the findings “spectacular,” a “landmark trial,” and a “winner.”

The study also set an new, lower floor for the level of albuminuria that can be usefully treated with dapagliflozin (Farxiga) by enrolling patients with a urinary albumin-to-creatinine ratio as low as 200 mg/g; the previous lower limit had been 300 mg/g, noted Dr. Mathieu. The new findings pose challenges to guideline writers, regulators who approve drug labels, and payers to a quickly make changes that will bring dapagliflozin to a wider number of patients with CKD.

Once the full DAPA-CKD results are reported, “it will change practice, and push the eGFR needle down” to as low as 25. It will also lower the albuminuria threshold for using dapagliflozin or other drugs in the class, commented David Z.I. Cherney, MD, a nephrologist at the University of Toronto. “It’s just one study,” he admitted, but the consistent renal benefits seen across several studies involving all four drugs in the SGLT2 inhibitor class will help hasten this change in identifying treatable patients, as well as expand the drug class to patients with CKD but no type 2 diabetes (T2D).

“I don’t think we’ve ever had stronger evidence” for drugs that can benefit both heart and renal function, plus the drug class is “very safe, and really easy to start” and maintain in patients, Dr. Cherney said in an interview. “It’s wonderful for these patients that we now have something new for treatment,” a drug with a “very favorable benefit-to-risk ratio.”
 

Results show many dapagliflozin benefits

While this broadening of the range of patients proven to tolerate and benefit from an SGLT2 inhibitor was an important consequence of DAPA-CKD, the study’s primary finding – that dapagliflozin was as safe and effective for slowing CKD progression in patients regardless of whether they also had T2D – will have an even bigger impact on expanding the target patient population. Showing efficacy in patients with CKD but without a T2D etiology, the status of about a third of the enrolled 4,304 patients, makes this treatment an option for “millions” of additional patients worldwide, said Dr. Heerspink. “These are the most common patients nephrologists see.” A major challenge now will be to do a better job finding patients with CKD who could benefit from dapagliflozin.

DAPA-CKD enrolled CKD patients based primarily on prespecified albuminuria and eGFR levels at more than 300 centers in 34 countries, including the United States. Virtually all patients, 97%, were on the only treatment now available with proven efficacy for slowing CKD, either an ACE inhibitor or an angiotensin receptor blocker. The small number of patients not on one of these drugs was because of poor tolerance.

The study’s primary endpoint was the combined rate of cardiovascular death, renal death, end-stage renal disease, or a drop in eGFR of at least 50% from baseline. This occurred in 14.5% of patients who received placebo and in 9.2% of those who received dapagliflozin during a median follow-up of 2.4 years, a highly significant 39% relative risk reduction. Concurrently with the report at the virtual meeting the results also appeared online in the New England Journal of Medicine. This 5.3% cut in the absolute rate of the combined, primary adverse outcome converted into a number needed to treat of 19 to prevent 1 event during 2.4 years, a “much lower” number needed to treat than reported for renin-angiotensin system inhibitors in these types of patients, Dr. Heerspink said.

Notable positive secondary outcomes included a significant 31% relative cut (a 2% absolute decline) in all-cause mortality, “a major highlight” of the findings, Dr. Heerspink said. Dapagliflozin treatment also linked with a significant 29% relative cut in the incidence of cardiovascular death or hospitalization for heart failure.

“Cardiovascular disease is the most common cause of death in patients with CKD,” explained David C. Wheeler, MD, a coinvestigator on the study and professor of kidney medicine at University College London. “The heart and kidney are intertwined. This is about cardiorenal disease.”

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Heerspink has been a consultant to and received research funding from AstraZeneca. He has also received personal fees from Mundipharma and Novo Nordisk, and he has also served as consultant to several other companies with the honoraria being paid to his institution. Dr. Mathieu has had relationships with AstraZeneca and several other companies. Dr. Cherney has been a consultant to and has received research funding from AstraZeneca and several other companies. Dr. Wheeler has received personal fees from AstraZeneca and from several other companies.

[email protected]

SOURCE: Heerspink HJL et al. EASD 2020 and N Engl J Med. 2020 Sep 24. doi: 10.1056/NEJMoa2024816.

The dramatically positive safety and efficacy results from the DAPA-CKD trial, which showed that treatment with the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin significantly cut both chronic kidney disease progression and all-cause death in patients with or without type 2 diabetes, were also notable for broadening the population of patients eligible for this treatment to those in the upper range of stage 4 CKD.

Courtesy European Society of Cardiology

Of the 4,304 CKD patients enrolled in DAPA-CKD, 624 (14%) had an estimated glomerular filtration rate (eGFR) of 25-29 mL/min per 1.73m², an unprecedented population to receive a drug from the SGLT2 inhibitor class in a reported study. The results provided definitive evidence for efficacy and safety in this range of renal function, said Hiddo J.L. Heerspink, Ph.D., at the virtual annual meeting of the European Association for the Study of Diabetes.

Until now, the widely accepted lowest level for starting an SGLT2 inhibitor in routine practice has been an eGFR as low as 30 mL/min per 1.73 m².
 

Using SGLT2 inhibitors when eGFR is as low as 25

“It’s time to reduce the eGFR level for initiating an SGLT2 inhibitor to as low as 25,” said Dr. Heerspink, a professor of clinical pharmacology at the University of Groningen (the Netherlands).

While conceding that this is primarily a decision to be made by guideline writers and regulatory bodies, he declared what he believed was established by the DAPA-CKD findings: “We’ve shown that dapagliflozin can be safely used in these patients. It is effective across the spectrum of kidney function.”

Other experts not associated with the study agreed.

Sara Freeman/MDedge News

The trial researchers were “brave” to enroll patients with eGFRs as low as 25 mL/min per 1.73 m², and “we urgently need these agents in patients with an eGFR this low,” commented Chantal Mathieu, MD, an endocrinologist and professor of medicine at Catholic University in Leuven, Belgium, and designated discussant for the report. Overall, she called the findings “spectacular,” a “landmark trial,” and a “winner.”

The study also set an new, lower floor for the level of albuminuria that can be usefully treated with dapagliflozin (Farxiga) by enrolling patients with a urinary albumin-to-creatinine ratio as low as 200 mg/g; the previous lower limit had been 300 mg/g, noted Dr. Mathieu. The new findings pose challenges to guideline writers, regulators who approve drug labels, and payers to a quickly make changes that will bring dapagliflozin to a wider number of patients with CKD.

Once the full DAPA-CKD results are reported, “it will change practice, and push the eGFR needle down” to as low as 25. It will also lower the albuminuria threshold for using dapagliflozin or other drugs in the class, commented David Z.I. Cherney, MD, a nephrologist at the University of Toronto. “It’s just one study,” he admitted, but the consistent renal benefits seen across several studies involving all four drugs in the SGLT2 inhibitor class will help hasten this change in identifying treatable patients, as well as expand the drug class to patients with CKD but no type 2 diabetes (T2D).

“I don’t think we’ve ever had stronger evidence” for drugs that can benefit both heart and renal function, plus the drug class is “very safe, and really easy to start” and maintain in patients, Dr. Cherney said in an interview. “It’s wonderful for these patients that we now have something new for treatment,” a drug with a “very favorable benefit-to-risk ratio.”
 

Results show many dapagliflozin benefits

While this broadening of the range of patients proven to tolerate and benefit from an SGLT2 inhibitor was an important consequence of DAPA-CKD, the study’s primary finding – that dapagliflozin was as safe and effective for slowing CKD progression in patients regardless of whether they also had T2D – will have an even bigger impact on expanding the target patient population. Showing efficacy in patients with CKD but without a T2D etiology, the status of about a third of the enrolled 4,304 patients, makes this treatment an option for “millions” of additional patients worldwide, said Dr. Heerspink. “These are the most common patients nephrologists see.” A major challenge now will be to do a better job finding patients with CKD who could benefit from dapagliflozin.

DAPA-CKD enrolled CKD patients based primarily on prespecified albuminuria and eGFR levels at more than 300 centers in 34 countries, including the United States. Virtually all patients, 97%, were on the only treatment now available with proven efficacy for slowing CKD, either an ACE inhibitor or an angiotensin receptor blocker. The small number of patients not on one of these drugs was because of poor tolerance.

The study’s primary endpoint was the combined rate of cardiovascular death, renal death, end-stage renal disease, or a drop in eGFR of at least 50% from baseline. This occurred in 14.5% of patients who received placebo and in 9.2% of those who received dapagliflozin during a median follow-up of 2.4 years, a highly significant 39% relative risk reduction. Concurrently with the report at the virtual meeting the results also appeared online in the New England Journal of Medicine. This 5.3% cut in the absolute rate of the combined, primary adverse outcome converted into a number needed to treat of 19 to prevent 1 event during 2.4 years, a “much lower” number needed to treat than reported for renin-angiotensin system inhibitors in these types of patients, Dr. Heerspink said.

Notable positive secondary outcomes included a significant 31% relative cut (a 2% absolute decline) in all-cause mortality, “a major highlight” of the findings, Dr. Heerspink said. Dapagliflozin treatment also linked with a significant 29% relative cut in the incidence of cardiovascular death or hospitalization for heart failure.

“Cardiovascular disease is the most common cause of death in patients with CKD,” explained David C. Wheeler, MD, a coinvestigator on the study and professor of kidney medicine at University College London. “The heart and kidney are intertwined. This is about cardiorenal disease.”

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Heerspink has been a consultant to and received research funding from AstraZeneca. He has also received personal fees from Mundipharma and Novo Nordisk, and he has also served as consultant to several other companies with the honoraria being paid to his institution. Dr. Mathieu has had relationships with AstraZeneca and several other companies. Dr. Cherney has been a consultant to and has received research funding from AstraZeneca and several other companies. Dr. Wheeler has received personal fees from AstraZeneca and from several other companies.

[email protected]

SOURCE: Heerspink HJL et al. EASD 2020 and N Engl J Med. 2020 Sep 24. doi: 10.1056/NEJMoa2024816.