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Benign adrenal tumors linked to hypertension, type 2 diabetes
In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.
The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.
“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement.
Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.
All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
MACS more common than previously thought
The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”
The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.
Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.
Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.
Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.
There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
Increasing cortisol levels linked with cardiometabolic disease
Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate.
Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.
People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.
The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.
Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
Determine the consequences of cortisol secretion
“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.
But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.
Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.
The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.
A version of this article first appeared on Medscape.com.
In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.
The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.
“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement.
Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.
All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
MACS more common than previously thought
The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”
The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.
Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.
Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.
Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.
There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
Increasing cortisol levels linked with cardiometabolic disease
Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate.
Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.
People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.
The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.
Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
Determine the consequences of cortisol secretion
“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.
But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.
Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.
The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.
A version of this article first appeared on Medscape.com.
In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.
The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.
“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement.
Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.
All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
MACS more common than previously thought
The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”
The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.
Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.
Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.
Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.
There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
Increasing cortisol levels linked with cardiometabolic disease
Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate.
Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.
People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.
The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.
Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
Determine the consequences of cortisol secretion
“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.
But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.
Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.
The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
FDA approves levoketoconazole for Cushing syndrome
The Food and Drug Administration has approved levoketoconazole (Recorlev, Xeris Biopharma) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not possible or was not curative.
Endogenous Cushing syndrome is a relatively rare condition characterized by chronically elevated cortisol levels, typically arising from a benign pituitary tumor. Left untreated, it can lead to reproductive problems and hirsutism in women, as well as serious complications, including diabetes, hypertension, tissue fragility, and mood disorders. Half of patients will die within 5 years if left untreated.
Levoketoconazole inhibits cortisol synthesis. The FDA approval was based on efficacy and safety data from two phase 3 studies involving a total of 166 patients with endogenous Cushing syndrome. In both the open-label, single-arm SONICS study and the randomized, placebo-controlled LOGICS trial, the drug significantly reduced and normalized mean urinary free cortisol levels and improved several secondary endpoints. The ongoing open-label OPTICS study will gather long-term data.
The Recorlev label includes boxed warnings about the potential for life-threatening hepatotoxicity and QT prolongation. Prior to and during treatment, patients should undergo liver enzyme testing, ECG, and correction of hypokalemia and hypomagnesemia.
The most common adverse reactions (occurring in less than 20%) include nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema.
“Cushing syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options ... We are excited to see that the long and complicated path of rare drug development has reached FDA approval on a new therapeutic option for our underserved Cushing’s community,” Leslie Edwin, president of the Cushing’s Support & Research Foundation, said in a Xeris statement.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved levoketoconazole (Recorlev, Xeris Biopharma) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not possible or was not curative.
Endogenous Cushing syndrome is a relatively rare condition characterized by chronically elevated cortisol levels, typically arising from a benign pituitary tumor. Left untreated, it can lead to reproductive problems and hirsutism in women, as well as serious complications, including diabetes, hypertension, tissue fragility, and mood disorders. Half of patients will die within 5 years if left untreated.
Levoketoconazole inhibits cortisol synthesis. The FDA approval was based on efficacy and safety data from two phase 3 studies involving a total of 166 patients with endogenous Cushing syndrome. In both the open-label, single-arm SONICS study and the randomized, placebo-controlled LOGICS trial, the drug significantly reduced and normalized mean urinary free cortisol levels and improved several secondary endpoints. The ongoing open-label OPTICS study will gather long-term data.
The Recorlev label includes boxed warnings about the potential for life-threatening hepatotoxicity and QT prolongation. Prior to and during treatment, patients should undergo liver enzyme testing, ECG, and correction of hypokalemia and hypomagnesemia.
The most common adverse reactions (occurring in less than 20%) include nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema.
“Cushing syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options ... We are excited to see that the long and complicated path of rare drug development has reached FDA approval on a new therapeutic option for our underserved Cushing’s community,” Leslie Edwin, president of the Cushing’s Support & Research Foundation, said in a Xeris statement.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved levoketoconazole (Recorlev, Xeris Biopharma) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not possible or was not curative.
Endogenous Cushing syndrome is a relatively rare condition characterized by chronically elevated cortisol levels, typically arising from a benign pituitary tumor. Left untreated, it can lead to reproductive problems and hirsutism in women, as well as serious complications, including diabetes, hypertension, tissue fragility, and mood disorders. Half of patients will die within 5 years if left untreated.
Levoketoconazole inhibits cortisol synthesis. The FDA approval was based on efficacy and safety data from two phase 3 studies involving a total of 166 patients with endogenous Cushing syndrome. In both the open-label, single-arm SONICS study and the randomized, placebo-controlled LOGICS trial, the drug significantly reduced and normalized mean urinary free cortisol levels and improved several secondary endpoints. The ongoing open-label OPTICS study will gather long-term data.
The Recorlev label includes boxed warnings about the potential for life-threatening hepatotoxicity and QT prolongation. Prior to and during treatment, patients should undergo liver enzyme testing, ECG, and correction of hypokalemia and hypomagnesemia.
The most common adverse reactions (occurring in less than 20%) include nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema.
“Cushing syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options ... We are excited to see that the long and complicated path of rare drug development has reached FDA approval on a new therapeutic option for our underserved Cushing’s community,” Leslie Edwin, president of the Cushing’s Support & Research Foundation, said in a Xeris statement.
A version of this article first appeared on Medscape.com.
ADA standards of care 2022: Screen more, personalize, use technology
The American Diabetes Association’s updated clinical recommendations for 2022 call for wider population screening, along with furthering the trends toward individualization of care use of diabetes technology.
The summary of changes from 2021 spans four pages. “Diabetes is a really dynamic field so there is a lot to update which is good. It means progress,” ADA chief science and medical officer Robert A. Gabbay, MD, PhD, told this news organization.
The ADA Standards of Medical Care in Diabetes – 2022 was published Dec. 20, 2021, online as a supplement to Diabetes Care.
Screening widened by age, in pregnancy, and for type 1 diabetes
One dramatic change is a drop in age to begin screening all people for prediabetes and diabetes from 45 years to 35 years, regardless of risk factors such as obesity.
“Sadly, there are increasing numbers of people with diabetes and developing diabetes younger,” Dr. Gabbay said.
In August 2021, the U.S. Preventive Services Task Force dropped its recommended age of diabetes screening from 40 to 35 years for people with overweight or obesity, but not universally, as ADA now has.
The ADA made its recommendation independently, Dr. Gabbay noted.
The recommendation for testing pregnant women early in gestation (<15 weeks) for preexisting diabetes was also expanded, from just those with risk factors to consideration of testing all women for undiagnosed diabetes at the time they’re planning pregnancy, and if not then, at the first prenatal visit. Screening for gestational diabetes is then performed at 24-28 weeks.
Again, this is caused by increasing diabetes onset at younger ages, Dr. Gabbay said. “We’re well aware that the number of women who have diabetes and don’t know it and become pregnant is significant and therefore screening early on is important.”
New guidance regarding autoantibody screening in adults suspected of having type 1 diabetes and genetic testing for those who don’t fit typical criteria for either of the two main types are based on the ADA/European Association for the Study of Diabetes joint consensus statement on type 1 diabetes in adults.
Individualization of care based on comorbidities, other factors
The concept of individualization of care in diabetes has been emphasized for several years now, but continues to be enhanced with new data and newly available management tools.
Regarding management of type 2 diabetes, several charts have been included to help guide decision-making.
One lists drug-specific and patient factors, including comorbidities, to consider when selecting glucose-lowering medications. A new table depicts a building with four “pillars,” for complication risk reduction, including management of blood pressure, lipids, and glucose, as well as use of agents with cardiovascular and kidney benefit.
“On the type 2 side, the choice of therapy is really guided by several factors. We lay them out in a nice diagram. ... A lot of useful information there compares classes of drugs in order to help clinicians make decisions on what would be the appropriate therapy for a given individual,” Dr. Gabbay said.
An algorithm for pharmacologic treatment includes considerations of weight, hypoglycemia, and cost. Tables are also provided listing average wholesale prices of insulins and noninsulin medications.
A section now entitled “Obesity and weight management for the prevention and treatment of type 2 diabetes” has added content regarding the importance of addressing obesity in diabetes, particularly in the context of the COVID-19 pandemic, and the addition of semaglutide as an approved obesity treatment.
“What we hope is that this engenders a shared decision-making process with the patient to identify what the goals are and then choose the appropriate therapy for those goals,” Dr. Gabbay said.
New information has also been added about management of nonalcoholic fatty liver disease. “I think that’s one of the unrecognized and unaddressed complications of diabetes that we’ll see in the future, particularly as new therapies come out,” Dr. Gabbay predicted.
The section on cardiovascular disease and risk management, endorsed for the fourth year in a row by the American College of Cardiology, includes several new recommendations, including diagnosis of hypertension at a single visit if blood pressure is 180/110 mm Hg or greater, and individualization of blood pressure targets.
Chronic kidney disease management has now been separated from other microvascular complications into a standalone section, with several new updates. Retinopathy, neuropathy, and foot care remain combined in one section.
Diabetes technology: Rapidly evolving, access an issue
The new technology section “doubles down on the time in [normal glucose] range (TIR) concept,” but also emphasizes the importance of time below range.
“When we see that, we need to make a therapeutic change. We were concerned that as there’s more and more information and numbers, users might not pick up on what’s important,” Dr. Gabbay noted.
The new standards also provides greater affirmation of the value of continuous glucose monitoring (CGM) for people with both type 1 and type 2 diabetes at any age, with individualized choice of devices.
Access to technology is a “big issue, and something the ADA has really been fighting for, particularly in terms of health disparities,” Dr. Gabbay said, noting that ADA has a new Health Equity Now platform, which includes a “bill of rights” calling for all patients with diabetes to have access to state-of-the-art technologies, including CGM.
Overall, he said, “I think the big picture is diabetes continues to evolve and advance. After careful review of the literature, the standards of care identifies at least four big areas where there are some changes that clinicians need to know about: screening, how to individualize treatment, considerations of comorbidities, and the important role that technology plays.”
Dr. Gabbay is an employee of the ADA.
A version of this article first appeared on Medscape.com.
The American Diabetes Association’s updated clinical recommendations for 2022 call for wider population screening, along with furthering the trends toward individualization of care use of diabetes technology.
The summary of changes from 2021 spans four pages. “Diabetes is a really dynamic field so there is a lot to update which is good. It means progress,” ADA chief science and medical officer Robert A. Gabbay, MD, PhD, told this news organization.
The ADA Standards of Medical Care in Diabetes – 2022 was published Dec. 20, 2021, online as a supplement to Diabetes Care.
Screening widened by age, in pregnancy, and for type 1 diabetes
One dramatic change is a drop in age to begin screening all people for prediabetes and diabetes from 45 years to 35 years, regardless of risk factors such as obesity.
“Sadly, there are increasing numbers of people with diabetes and developing diabetes younger,” Dr. Gabbay said.
In August 2021, the U.S. Preventive Services Task Force dropped its recommended age of diabetes screening from 40 to 35 years for people with overweight or obesity, but not universally, as ADA now has.
The ADA made its recommendation independently, Dr. Gabbay noted.
The recommendation for testing pregnant women early in gestation (<15 weeks) for preexisting diabetes was also expanded, from just those with risk factors to consideration of testing all women for undiagnosed diabetes at the time they’re planning pregnancy, and if not then, at the first prenatal visit. Screening for gestational diabetes is then performed at 24-28 weeks.
Again, this is caused by increasing diabetes onset at younger ages, Dr. Gabbay said. “We’re well aware that the number of women who have diabetes and don’t know it and become pregnant is significant and therefore screening early on is important.”
New guidance regarding autoantibody screening in adults suspected of having type 1 diabetes and genetic testing for those who don’t fit typical criteria for either of the two main types are based on the ADA/European Association for the Study of Diabetes joint consensus statement on type 1 diabetes in adults.
Individualization of care based on comorbidities, other factors
The concept of individualization of care in diabetes has been emphasized for several years now, but continues to be enhanced with new data and newly available management tools.
Regarding management of type 2 diabetes, several charts have been included to help guide decision-making.
One lists drug-specific and patient factors, including comorbidities, to consider when selecting glucose-lowering medications. A new table depicts a building with four “pillars,” for complication risk reduction, including management of blood pressure, lipids, and glucose, as well as use of agents with cardiovascular and kidney benefit.
“On the type 2 side, the choice of therapy is really guided by several factors. We lay them out in a nice diagram. ... A lot of useful information there compares classes of drugs in order to help clinicians make decisions on what would be the appropriate therapy for a given individual,” Dr. Gabbay said.
An algorithm for pharmacologic treatment includes considerations of weight, hypoglycemia, and cost. Tables are also provided listing average wholesale prices of insulins and noninsulin medications.
A section now entitled “Obesity and weight management for the prevention and treatment of type 2 diabetes” has added content regarding the importance of addressing obesity in diabetes, particularly in the context of the COVID-19 pandemic, and the addition of semaglutide as an approved obesity treatment.
“What we hope is that this engenders a shared decision-making process with the patient to identify what the goals are and then choose the appropriate therapy for those goals,” Dr. Gabbay said.
New information has also been added about management of nonalcoholic fatty liver disease. “I think that’s one of the unrecognized and unaddressed complications of diabetes that we’ll see in the future, particularly as new therapies come out,” Dr. Gabbay predicted.
The section on cardiovascular disease and risk management, endorsed for the fourth year in a row by the American College of Cardiology, includes several new recommendations, including diagnosis of hypertension at a single visit if blood pressure is 180/110 mm Hg or greater, and individualization of blood pressure targets.
Chronic kidney disease management has now been separated from other microvascular complications into a standalone section, with several new updates. Retinopathy, neuropathy, and foot care remain combined in one section.
Diabetes technology: Rapidly evolving, access an issue
The new technology section “doubles down on the time in [normal glucose] range (TIR) concept,” but also emphasizes the importance of time below range.
“When we see that, we need to make a therapeutic change. We were concerned that as there’s more and more information and numbers, users might not pick up on what’s important,” Dr. Gabbay noted.
The new standards also provides greater affirmation of the value of continuous glucose monitoring (CGM) for people with both type 1 and type 2 diabetes at any age, with individualized choice of devices.
Access to technology is a “big issue, and something the ADA has really been fighting for, particularly in terms of health disparities,” Dr. Gabbay said, noting that ADA has a new Health Equity Now platform, which includes a “bill of rights” calling for all patients with diabetes to have access to state-of-the-art technologies, including CGM.
Overall, he said, “I think the big picture is diabetes continues to evolve and advance. After careful review of the literature, the standards of care identifies at least four big areas where there are some changes that clinicians need to know about: screening, how to individualize treatment, considerations of comorbidities, and the important role that technology plays.”
Dr. Gabbay is an employee of the ADA.
A version of this article first appeared on Medscape.com.
The American Diabetes Association’s updated clinical recommendations for 2022 call for wider population screening, along with furthering the trends toward individualization of care use of diabetes technology.
The summary of changes from 2021 spans four pages. “Diabetes is a really dynamic field so there is a lot to update which is good. It means progress,” ADA chief science and medical officer Robert A. Gabbay, MD, PhD, told this news organization.
The ADA Standards of Medical Care in Diabetes – 2022 was published Dec. 20, 2021, online as a supplement to Diabetes Care.
Screening widened by age, in pregnancy, and for type 1 diabetes
One dramatic change is a drop in age to begin screening all people for prediabetes and diabetes from 45 years to 35 years, regardless of risk factors such as obesity.
“Sadly, there are increasing numbers of people with diabetes and developing diabetes younger,” Dr. Gabbay said.
In August 2021, the U.S. Preventive Services Task Force dropped its recommended age of diabetes screening from 40 to 35 years for people with overweight or obesity, but not universally, as ADA now has.
The ADA made its recommendation independently, Dr. Gabbay noted.
The recommendation for testing pregnant women early in gestation (<15 weeks) for preexisting diabetes was also expanded, from just those with risk factors to consideration of testing all women for undiagnosed diabetes at the time they’re planning pregnancy, and if not then, at the first prenatal visit. Screening for gestational diabetes is then performed at 24-28 weeks.
Again, this is caused by increasing diabetes onset at younger ages, Dr. Gabbay said. “We’re well aware that the number of women who have diabetes and don’t know it and become pregnant is significant and therefore screening early on is important.”
New guidance regarding autoantibody screening in adults suspected of having type 1 diabetes and genetic testing for those who don’t fit typical criteria for either of the two main types are based on the ADA/European Association for the Study of Diabetes joint consensus statement on type 1 diabetes in adults.
Individualization of care based on comorbidities, other factors
The concept of individualization of care in diabetes has been emphasized for several years now, but continues to be enhanced with new data and newly available management tools.
Regarding management of type 2 diabetes, several charts have been included to help guide decision-making.
One lists drug-specific and patient factors, including comorbidities, to consider when selecting glucose-lowering medications. A new table depicts a building with four “pillars,” for complication risk reduction, including management of blood pressure, lipids, and glucose, as well as use of agents with cardiovascular and kidney benefit.
“On the type 2 side, the choice of therapy is really guided by several factors. We lay them out in a nice diagram. ... A lot of useful information there compares classes of drugs in order to help clinicians make decisions on what would be the appropriate therapy for a given individual,” Dr. Gabbay said.
An algorithm for pharmacologic treatment includes considerations of weight, hypoglycemia, and cost. Tables are also provided listing average wholesale prices of insulins and noninsulin medications.
A section now entitled “Obesity and weight management for the prevention and treatment of type 2 diabetes” has added content regarding the importance of addressing obesity in diabetes, particularly in the context of the COVID-19 pandemic, and the addition of semaglutide as an approved obesity treatment.
“What we hope is that this engenders a shared decision-making process with the patient to identify what the goals are and then choose the appropriate therapy for those goals,” Dr. Gabbay said.
New information has also been added about management of nonalcoholic fatty liver disease. “I think that’s one of the unrecognized and unaddressed complications of diabetes that we’ll see in the future, particularly as new therapies come out,” Dr. Gabbay predicted.
The section on cardiovascular disease and risk management, endorsed for the fourth year in a row by the American College of Cardiology, includes several new recommendations, including diagnosis of hypertension at a single visit if blood pressure is 180/110 mm Hg or greater, and individualization of blood pressure targets.
Chronic kidney disease management has now been separated from other microvascular complications into a standalone section, with several new updates. Retinopathy, neuropathy, and foot care remain combined in one section.
Diabetes technology: Rapidly evolving, access an issue
The new technology section “doubles down on the time in [normal glucose] range (TIR) concept,” but also emphasizes the importance of time below range.
“When we see that, we need to make a therapeutic change. We were concerned that as there’s more and more information and numbers, users might not pick up on what’s important,” Dr. Gabbay noted.
The new standards also provides greater affirmation of the value of continuous glucose monitoring (CGM) for people with both type 1 and type 2 diabetes at any age, with individualized choice of devices.
Access to technology is a “big issue, and something the ADA has really been fighting for, particularly in terms of health disparities,” Dr. Gabbay said, noting that ADA has a new Health Equity Now platform, which includes a “bill of rights” calling for all patients with diabetes to have access to state-of-the-art technologies, including CGM.
Overall, he said, “I think the big picture is diabetes continues to evolve and advance. After careful review of the literature, the standards of care identifies at least four big areas where there are some changes that clinicians need to know about: screening, how to individualize treatment, considerations of comorbidities, and the important role that technology plays.”
Dr. Gabbay is an employee of the ADA.
A version of this article first appeared on Medscape.com.
Inadequate routine diabetes screening common in HIV
, research shows.
“Despite known risk in this patient population, most patients were not up to date with routine preventative screenings,” report Maya Hardman, PharmD, and colleagues with Southwest CARE Center, in Santa Fe, New Mexico, in research presented at the United States Conference on HIV/AIDS (USCHA) 2021 Annual Meeting.
“Routine preventative screenings can help identify chronic complications of diabetes early, if performed at the recommended intervals,” they write.
People with HIV are known to be at an increased risk of diabetes and the long-term complications of the disease, making the need for routine screening to prevent such complications all the more pressing due to their higher-risk health status.
Among the key routine diabetes care quality measures recommended by the Healthcare Effectiveness Data and Information Set (HEDIS) for people with HIV are testing for A1c once every 3 months, foot and eye exams every 12 months, urine albumin creatinine ratio (UACR) screenings every 12 months, and two controlled blood pressure readings every 12 months.
To investigate the rates of adherence to the HEDIS screening recommendations and identify predictors of poor compliance among people with HIV, Dr. Hardman and her colleagues evaluated data on 121 adult patients at the Southwest CARE Center who had been diagnosed with diabetes and HIV and were treated between 2019 and 2020.
The patients had a mean age of 57.5, and 9% were female. Their mean duration of being HIV positive was 19.8 years, and they had an intermediate Atherosclerotic Cardiovascular Disease (ASCVD) risk score of 17.08%.
Despite their known diagnoses of having diabetes, as many as 93.4% were found not to be up to date on their routine preventive screenings.
Of the 121 patients, only 30 had received the recommended A1c screenings, 37 had the recommended UACR screenings, and just 18 had received the recommended foot exam screenings.
Only blood pressure screenings, reported in 90 of the 121 patients, were up to date in the majority of patients in the group.
In looking at factors associated with compliance with A1c screening, only age (OR, 0.95; P = .04) was a significant predictor.
The authors pointed out that routine screenings for diabetes complications are relatively easy to implement.
“Screening for these chronic complications is minimally invasive and can be provided by individuals trained in diabetes management during routine clinic appointments.”
The team’s ongoing research is evaluating the potential benefits of clinical pharmacy services in assisting with the screenings for patients with HIV.
Research underscoring the increased risk and poorer treatment outcomes of diabetes in people with HIV include a study comparing 337 people with HIV in 2005 with a cohort of 338 participants in 2015.
The study showed the prevalence of type 2 diabetes had increased to 15.1% in 2015 from 6.8% 10 years earlier, for a relative risk of 2.4 compared with the general population.
“The alarmingly high prevalence of type 2 diabetes in HIV requires improved screening, targeted to older patients and those with a longer duration of exposure to antiretrovirals,” the authors wrote.
“Effective diabetes prevention and management strategies are needed urgently to reduce this risk; such interventions should target both conventional risk factors, such as abdominal obesity and HIV-specific risk factors such as weight gain following initiation of antiretrovirals.”
Of note, the 2015 cohort was significantly older and had higher BMI and higher hypertension than the 2005 cohort.
First author Alastair Duncan, PhD, principal dietitian at Guy’s & St. Thomas’ Hospital and lecturer, King’s College London, noted that since that 2015 study was published, concerns particularly with weight gain in the HIV population have only increased.
“Weight gain appears to be more of an issue [now],” he told this news organization in an interview.
“As in the general population, people living with HIV experienced significant weight gain during COVID-related lockdowns. Added to the high number of people living with HIV being treated with integrase inhibitors, weight gain remains a challenge.”
Meanwhile, “there are not enough studies comparing people living with HIV with the general population,” Dr. Duncan added. “We need to conduct studies where participants are matched.”
Sudipa Sarkar, MD, who co-authored a report on the issue of diabetes and HIV this year but was not involved in the study presented at USCHA, noted that the setting of care could play an important role in the quality of screening for diabetes that people with HIV receive.
“It may depend on factors such as whether a patient is being followed regularly by an HIV care provider and the larger health care system that the patient is in,” Dr. Sarkar, an assistant professor of medicine at Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, told this news organization.
“For example, one might find differences between a patient being seen in a managed care group versus not.”
The issue of how the strikingly high rates of inadequate screening in the current study compare with routine screening in the general diabetes population “is a good question and warrants more research,” she said.
The authors and Dr. Sarkar have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, research shows.
“Despite known risk in this patient population, most patients were not up to date with routine preventative screenings,” report Maya Hardman, PharmD, and colleagues with Southwest CARE Center, in Santa Fe, New Mexico, in research presented at the United States Conference on HIV/AIDS (USCHA) 2021 Annual Meeting.
“Routine preventative screenings can help identify chronic complications of diabetes early, if performed at the recommended intervals,” they write.
People with HIV are known to be at an increased risk of diabetes and the long-term complications of the disease, making the need for routine screening to prevent such complications all the more pressing due to their higher-risk health status.
Among the key routine diabetes care quality measures recommended by the Healthcare Effectiveness Data and Information Set (HEDIS) for people with HIV are testing for A1c once every 3 months, foot and eye exams every 12 months, urine albumin creatinine ratio (UACR) screenings every 12 months, and two controlled blood pressure readings every 12 months.
To investigate the rates of adherence to the HEDIS screening recommendations and identify predictors of poor compliance among people with HIV, Dr. Hardman and her colleagues evaluated data on 121 adult patients at the Southwest CARE Center who had been diagnosed with diabetes and HIV and were treated between 2019 and 2020.
The patients had a mean age of 57.5, and 9% were female. Their mean duration of being HIV positive was 19.8 years, and they had an intermediate Atherosclerotic Cardiovascular Disease (ASCVD) risk score of 17.08%.
Despite their known diagnoses of having diabetes, as many as 93.4% were found not to be up to date on their routine preventive screenings.
Of the 121 patients, only 30 had received the recommended A1c screenings, 37 had the recommended UACR screenings, and just 18 had received the recommended foot exam screenings.
Only blood pressure screenings, reported in 90 of the 121 patients, were up to date in the majority of patients in the group.
In looking at factors associated with compliance with A1c screening, only age (OR, 0.95; P = .04) was a significant predictor.
The authors pointed out that routine screenings for diabetes complications are relatively easy to implement.
“Screening for these chronic complications is minimally invasive and can be provided by individuals trained in diabetes management during routine clinic appointments.”
The team’s ongoing research is evaluating the potential benefits of clinical pharmacy services in assisting with the screenings for patients with HIV.
Research underscoring the increased risk and poorer treatment outcomes of diabetes in people with HIV include a study comparing 337 people with HIV in 2005 with a cohort of 338 participants in 2015.
The study showed the prevalence of type 2 diabetes had increased to 15.1% in 2015 from 6.8% 10 years earlier, for a relative risk of 2.4 compared with the general population.
“The alarmingly high prevalence of type 2 diabetes in HIV requires improved screening, targeted to older patients and those with a longer duration of exposure to antiretrovirals,” the authors wrote.
“Effective diabetes prevention and management strategies are needed urgently to reduce this risk; such interventions should target both conventional risk factors, such as abdominal obesity and HIV-specific risk factors such as weight gain following initiation of antiretrovirals.”
Of note, the 2015 cohort was significantly older and had higher BMI and higher hypertension than the 2005 cohort.
First author Alastair Duncan, PhD, principal dietitian at Guy’s & St. Thomas’ Hospital and lecturer, King’s College London, noted that since that 2015 study was published, concerns particularly with weight gain in the HIV population have only increased.
“Weight gain appears to be more of an issue [now],” he told this news organization in an interview.
“As in the general population, people living with HIV experienced significant weight gain during COVID-related lockdowns. Added to the high number of people living with HIV being treated with integrase inhibitors, weight gain remains a challenge.”
Meanwhile, “there are not enough studies comparing people living with HIV with the general population,” Dr. Duncan added. “We need to conduct studies where participants are matched.”
Sudipa Sarkar, MD, who co-authored a report on the issue of diabetes and HIV this year but was not involved in the study presented at USCHA, noted that the setting of care could play an important role in the quality of screening for diabetes that people with HIV receive.
“It may depend on factors such as whether a patient is being followed regularly by an HIV care provider and the larger health care system that the patient is in,” Dr. Sarkar, an assistant professor of medicine at Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, told this news organization.
“For example, one might find differences between a patient being seen in a managed care group versus not.”
The issue of how the strikingly high rates of inadequate screening in the current study compare with routine screening in the general diabetes population “is a good question and warrants more research,” she said.
The authors and Dr. Sarkar have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, research shows.
“Despite known risk in this patient population, most patients were not up to date with routine preventative screenings,” report Maya Hardman, PharmD, and colleagues with Southwest CARE Center, in Santa Fe, New Mexico, in research presented at the United States Conference on HIV/AIDS (USCHA) 2021 Annual Meeting.
“Routine preventative screenings can help identify chronic complications of diabetes early, if performed at the recommended intervals,” they write.
People with HIV are known to be at an increased risk of diabetes and the long-term complications of the disease, making the need for routine screening to prevent such complications all the more pressing due to their higher-risk health status.
Among the key routine diabetes care quality measures recommended by the Healthcare Effectiveness Data and Information Set (HEDIS) for people with HIV are testing for A1c once every 3 months, foot and eye exams every 12 months, urine albumin creatinine ratio (UACR) screenings every 12 months, and two controlled blood pressure readings every 12 months.
To investigate the rates of adherence to the HEDIS screening recommendations and identify predictors of poor compliance among people with HIV, Dr. Hardman and her colleagues evaluated data on 121 adult patients at the Southwest CARE Center who had been diagnosed with diabetes and HIV and were treated between 2019 and 2020.
The patients had a mean age of 57.5, and 9% were female. Their mean duration of being HIV positive was 19.8 years, and they had an intermediate Atherosclerotic Cardiovascular Disease (ASCVD) risk score of 17.08%.
Despite their known diagnoses of having diabetes, as many as 93.4% were found not to be up to date on their routine preventive screenings.
Of the 121 patients, only 30 had received the recommended A1c screenings, 37 had the recommended UACR screenings, and just 18 had received the recommended foot exam screenings.
Only blood pressure screenings, reported in 90 of the 121 patients, were up to date in the majority of patients in the group.
In looking at factors associated with compliance with A1c screening, only age (OR, 0.95; P = .04) was a significant predictor.
The authors pointed out that routine screenings for diabetes complications are relatively easy to implement.
“Screening for these chronic complications is minimally invasive and can be provided by individuals trained in diabetes management during routine clinic appointments.”
The team’s ongoing research is evaluating the potential benefits of clinical pharmacy services in assisting with the screenings for patients with HIV.
Research underscoring the increased risk and poorer treatment outcomes of diabetes in people with HIV include a study comparing 337 people with HIV in 2005 with a cohort of 338 participants in 2015.
The study showed the prevalence of type 2 diabetes had increased to 15.1% in 2015 from 6.8% 10 years earlier, for a relative risk of 2.4 compared with the general population.
“The alarmingly high prevalence of type 2 diabetes in HIV requires improved screening, targeted to older patients and those with a longer duration of exposure to antiretrovirals,” the authors wrote.
“Effective diabetes prevention and management strategies are needed urgently to reduce this risk; such interventions should target both conventional risk factors, such as abdominal obesity and HIV-specific risk factors such as weight gain following initiation of antiretrovirals.”
Of note, the 2015 cohort was significantly older and had higher BMI and higher hypertension than the 2005 cohort.
First author Alastair Duncan, PhD, principal dietitian at Guy’s & St. Thomas’ Hospital and lecturer, King’s College London, noted that since that 2015 study was published, concerns particularly with weight gain in the HIV population have only increased.
“Weight gain appears to be more of an issue [now],” he told this news organization in an interview.
“As in the general population, people living with HIV experienced significant weight gain during COVID-related lockdowns. Added to the high number of people living with HIV being treated with integrase inhibitors, weight gain remains a challenge.”
Meanwhile, “there are not enough studies comparing people living with HIV with the general population,” Dr. Duncan added. “We need to conduct studies where participants are matched.”
Sudipa Sarkar, MD, who co-authored a report on the issue of diabetes and HIV this year but was not involved in the study presented at USCHA, noted that the setting of care could play an important role in the quality of screening for diabetes that people with HIV receive.
“It may depend on factors such as whether a patient is being followed regularly by an HIV care provider and the larger health care system that the patient is in,” Dr. Sarkar, an assistant professor of medicine at Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, told this news organization.
“For example, one might find differences between a patient being seen in a managed care group versus not.”
The issue of how the strikingly high rates of inadequate screening in the current study compare with routine screening in the general diabetes population “is a good question and warrants more research,” she said.
The authors and Dr. Sarkar have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cancer-related thyroidectomy linked to increased diabetes risk
People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.
“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.
“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.
While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.
“A 40% increased risk of diabetes is a big surprise,” he said in an interview.
“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
U-shaped relationship between levothyroxine dose and diabetes risk
The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.
The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m2.
Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.
The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).
In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).
A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).
“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.
However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.
“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
Potential mechanisms
Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.
The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.
Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.
Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values.
“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
Control group should have had hypothyroidism
The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.
“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.
In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.
“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.
“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”
Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.
“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.
“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.
While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.
“A 40% increased risk of diabetes is a big surprise,” he said in an interview.
“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
U-shaped relationship between levothyroxine dose and diabetes risk
The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.
The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m2.
Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.
The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).
In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).
A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).
“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.
However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.
“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
Potential mechanisms
Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.
The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.
Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.
Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values.
“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
Control group should have had hypothyroidism
The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.
“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.
In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.
“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.
“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”
Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.
“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.
“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.
While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.
“A 40% increased risk of diabetes is a big surprise,” he said in an interview.
“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
U-shaped relationship between levothyroxine dose and diabetes risk
The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.
The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m2.
Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.
The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).
In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).
A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).
“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.
However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.
“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
Potential mechanisms
Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.
The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.
Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.
Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values.
“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
Control group should have had hypothyroidism
The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.
“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.
In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.
“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.
“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”
Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SGLT2 inhibitor use tied to fewer atrial arrhythmias
Patients with cardiac implantable electronic devices (CIEDs) who received treatment with an sodium-glucose cotransporter 2 inhibitor had significantly fewer atrial arrhythmia events, compared with those who never received such a drug, in a prospective analysis of nearly 14,000 patients with a device who were followed for an average of nearly 2 years.
The findings suggest that use of an agent from the class of SGLT2 inhibitors “is associated with a pronounced reduction in atrial arrhythmia burden and all-cause mortality in patients with a CIED in a real-world setting,” said Ilan Goldenberg, MD, at the American Heart Association scientific sessions. “These data indicate possible antiarrhythmic properties of SGLT2 inhibitors that are incremental to the beneficial effects of the drug on heart failure outcomes,” added Dr. Goldenberg, director of the Clinical Cardiovascular Research Center at the University of Rochester (N.Y.).
In a propensity score–matched analysis that included more than 5,000 of the enrolled patients with a CIED, treatment with an SGLT2 inhibitor was tied to a significant 23% relative reduction in atrial arrhythmia events and a 44% relative drop in all-cause death, he reported.
Effect mediated by reduced left atrial pressure?
“Other heart failure drugs have shown some decrease in the rate of sudden cardiac death, but this is the first [heart failure] drug to associate with a reduction in atrial arrhythmias,” Dr. Goldenberg noted. “We think that a reduction in left atrial pressure” produced by treatment with an SGLT2 inhibitor “may be linked to the reduction in atrial arrhythmias.”
The study did not show an association of SGLT2-inhibitor use and a change in ventricular arrhythmias, compared with patients with CIEDs who did not receive an agent from this class.
The findings suggest “expanding the possible indications for SGLT2 inhibitors,” commented Harriette G.C. Van Spall, MD, a cardiologist at McMaster University, Hamilton, Ont., who moderated the session where Dr. Goldenberg gave his report.
The study included 13,890 consecutive, prospectively enrolled patients who received a CIED during January 2015–April 2020 at any of five hospitals operated by either of two tertiary health care systems, one run by the University of Rochester and the second based at Sheba Medical Center in Tel HaShomer, Israel. The devices that made patients eligible for the study included permanent pacemakers, implantable cardioverter defibrillators, cardiac resynchronization therapy devices, and implantable cardiac monitors. A blinded adjudication committee composed of electrophysiologists identified the arrhythmic episodes.
At entry into the study (the time of device implantation), 12,992 patients were not receiving an SGLT2 inhibitor (94%) and 898 (6%) were receiving a drug from this class. Of those, 39% were on dapagliflozin (Farxiga), 35% were on empagliflozin (Jardiance), and 26% were on canagliflozin (Invokana).
Patients receiving an SGLT2 inhibitor at baseline were on average substantially younger than the patients not on this drug class (59 years vs. 69 years); they had a substantially higher prevalence of diabetes (78% vs. 25%), and ischemic cardiomyopathy (63% vs. 39%). Patients on an SGLT2 inhibitor at baseline also had more modestly higher prevalence rates of prior heart failure (38% vs. 31%), and hypertension (69% vs. 63%). Prevalence of a history of atrial fibrillation (AFib) was nearly the same in both groups: 31% in patients on an SGLT2 inhibitor and 35% in those not on these drugs.
The study’s primary endpoint was the total number of arrhythmia events during follow-up of 24,442 patient-years, during which patients exhibited 19,633 atrial arrhythmia events and 3,231 ventricular arrhythmia events.
1% absolute reduction in atrial arrhythmias
A multivariate analysis of the entire population – adjusted for baseline differences in age, diabetes, sex, and history of AFib – showed that treatment with an SGLT2 inhibitor at baseline was linked with a significant 24% relative reduction in incident atrial arrhythmia events, a significant 24% reduction in both atrial and ventricular arrhythmia events, and a 42% relative reduction in all-cause deaths, compared with no SGLT2-inhibitor treatment.
The only analyzed endpoint that showed no significant between-group difference was incidence of ventricular arrhythmias, which was a relative 7% lower in the SGLT2-inhibitor group.
On an absolute basis, treatment with an SGLT2 inhibitor was tied to about a 1% lower rate of atrial arrhythmia events per year, a reduction from a 2.5% rate in those not on an SGLT2 inhibitor to about a 1.5% rate in those taking this drug class.
A second, confirmatory analysis used propensity score matching to identify 5,323 patients not on an SGLT2 inhibitor at baseline who closely matched the 898 patients on an SGLT2 inhibitor. The multivariate modeling for this analysis also adjusted for age, diabetes, sex, and history of AFib.
The results of these analyses closely matched the calculations that used the entire study population. Relative to patients not on an SGLT2 inhibitor those on a drug from this class had 23% fewer atrial arrhythmias, 44% fewer total death, and 22% fewer atrial or ventricular arrhythmias, all significant differences. However, ventricular arrhythmias only reduced by a relative 5%, a nonsignificant difference.
In the propensity score–matched analysis, the absolute reduction in atrial arrhythmias in those on an SGLT2 inhibitor at baseline was roughly 1.3% fewer per year, compared with those not on this drug class.
The study was funded by an unrestricted grant to the University of Rochester from AstraZeneca, the company that markets the SGLT2 inhibitor dapagliflozin (Farxiga). Dr. Goldenberg and Dr. Van Spall had no disclosures.
Patients with cardiac implantable electronic devices (CIEDs) who received treatment with an sodium-glucose cotransporter 2 inhibitor had significantly fewer atrial arrhythmia events, compared with those who never received such a drug, in a prospective analysis of nearly 14,000 patients with a device who were followed for an average of nearly 2 years.
The findings suggest that use of an agent from the class of SGLT2 inhibitors “is associated with a pronounced reduction in atrial arrhythmia burden and all-cause mortality in patients with a CIED in a real-world setting,” said Ilan Goldenberg, MD, at the American Heart Association scientific sessions. “These data indicate possible antiarrhythmic properties of SGLT2 inhibitors that are incremental to the beneficial effects of the drug on heart failure outcomes,” added Dr. Goldenberg, director of the Clinical Cardiovascular Research Center at the University of Rochester (N.Y.).
In a propensity score–matched analysis that included more than 5,000 of the enrolled patients with a CIED, treatment with an SGLT2 inhibitor was tied to a significant 23% relative reduction in atrial arrhythmia events and a 44% relative drop in all-cause death, he reported.
Effect mediated by reduced left atrial pressure?
“Other heart failure drugs have shown some decrease in the rate of sudden cardiac death, but this is the first [heart failure] drug to associate with a reduction in atrial arrhythmias,” Dr. Goldenberg noted. “We think that a reduction in left atrial pressure” produced by treatment with an SGLT2 inhibitor “may be linked to the reduction in atrial arrhythmias.”
The study did not show an association of SGLT2-inhibitor use and a change in ventricular arrhythmias, compared with patients with CIEDs who did not receive an agent from this class.
The findings suggest “expanding the possible indications for SGLT2 inhibitors,” commented Harriette G.C. Van Spall, MD, a cardiologist at McMaster University, Hamilton, Ont., who moderated the session where Dr. Goldenberg gave his report.
The study included 13,890 consecutive, prospectively enrolled patients who received a CIED during January 2015–April 2020 at any of five hospitals operated by either of two tertiary health care systems, one run by the University of Rochester and the second based at Sheba Medical Center in Tel HaShomer, Israel. The devices that made patients eligible for the study included permanent pacemakers, implantable cardioverter defibrillators, cardiac resynchronization therapy devices, and implantable cardiac monitors. A blinded adjudication committee composed of electrophysiologists identified the arrhythmic episodes.
At entry into the study (the time of device implantation), 12,992 patients were not receiving an SGLT2 inhibitor (94%) and 898 (6%) were receiving a drug from this class. Of those, 39% were on dapagliflozin (Farxiga), 35% were on empagliflozin (Jardiance), and 26% were on canagliflozin (Invokana).
Patients receiving an SGLT2 inhibitor at baseline were on average substantially younger than the patients not on this drug class (59 years vs. 69 years); they had a substantially higher prevalence of diabetes (78% vs. 25%), and ischemic cardiomyopathy (63% vs. 39%). Patients on an SGLT2 inhibitor at baseline also had more modestly higher prevalence rates of prior heart failure (38% vs. 31%), and hypertension (69% vs. 63%). Prevalence of a history of atrial fibrillation (AFib) was nearly the same in both groups: 31% in patients on an SGLT2 inhibitor and 35% in those not on these drugs.
The study’s primary endpoint was the total number of arrhythmia events during follow-up of 24,442 patient-years, during which patients exhibited 19,633 atrial arrhythmia events and 3,231 ventricular arrhythmia events.
1% absolute reduction in atrial arrhythmias
A multivariate analysis of the entire population – adjusted for baseline differences in age, diabetes, sex, and history of AFib – showed that treatment with an SGLT2 inhibitor at baseline was linked with a significant 24% relative reduction in incident atrial arrhythmia events, a significant 24% reduction in both atrial and ventricular arrhythmia events, and a 42% relative reduction in all-cause deaths, compared with no SGLT2-inhibitor treatment.
The only analyzed endpoint that showed no significant between-group difference was incidence of ventricular arrhythmias, which was a relative 7% lower in the SGLT2-inhibitor group.
On an absolute basis, treatment with an SGLT2 inhibitor was tied to about a 1% lower rate of atrial arrhythmia events per year, a reduction from a 2.5% rate in those not on an SGLT2 inhibitor to about a 1.5% rate in those taking this drug class.
A second, confirmatory analysis used propensity score matching to identify 5,323 patients not on an SGLT2 inhibitor at baseline who closely matched the 898 patients on an SGLT2 inhibitor. The multivariate modeling for this analysis also adjusted for age, diabetes, sex, and history of AFib.
The results of these analyses closely matched the calculations that used the entire study population. Relative to patients not on an SGLT2 inhibitor those on a drug from this class had 23% fewer atrial arrhythmias, 44% fewer total death, and 22% fewer atrial or ventricular arrhythmias, all significant differences. However, ventricular arrhythmias only reduced by a relative 5%, a nonsignificant difference.
In the propensity score–matched analysis, the absolute reduction in atrial arrhythmias in those on an SGLT2 inhibitor at baseline was roughly 1.3% fewer per year, compared with those not on this drug class.
The study was funded by an unrestricted grant to the University of Rochester from AstraZeneca, the company that markets the SGLT2 inhibitor dapagliflozin (Farxiga). Dr. Goldenberg and Dr. Van Spall had no disclosures.
Patients with cardiac implantable electronic devices (CIEDs) who received treatment with an sodium-glucose cotransporter 2 inhibitor had significantly fewer atrial arrhythmia events, compared with those who never received such a drug, in a prospective analysis of nearly 14,000 patients with a device who were followed for an average of nearly 2 years.
The findings suggest that use of an agent from the class of SGLT2 inhibitors “is associated with a pronounced reduction in atrial arrhythmia burden and all-cause mortality in patients with a CIED in a real-world setting,” said Ilan Goldenberg, MD, at the American Heart Association scientific sessions. “These data indicate possible antiarrhythmic properties of SGLT2 inhibitors that are incremental to the beneficial effects of the drug on heart failure outcomes,” added Dr. Goldenberg, director of the Clinical Cardiovascular Research Center at the University of Rochester (N.Y.).
In a propensity score–matched analysis that included more than 5,000 of the enrolled patients with a CIED, treatment with an SGLT2 inhibitor was tied to a significant 23% relative reduction in atrial arrhythmia events and a 44% relative drop in all-cause death, he reported.
Effect mediated by reduced left atrial pressure?
“Other heart failure drugs have shown some decrease in the rate of sudden cardiac death, but this is the first [heart failure] drug to associate with a reduction in atrial arrhythmias,” Dr. Goldenberg noted. “We think that a reduction in left atrial pressure” produced by treatment with an SGLT2 inhibitor “may be linked to the reduction in atrial arrhythmias.”
The study did not show an association of SGLT2-inhibitor use and a change in ventricular arrhythmias, compared with patients with CIEDs who did not receive an agent from this class.
The findings suggest “expanding the possible indications for SGLT2 inhibitors,” commented Harriette G.C. Van Spall, MD, a cardiologist at McMaster University, Hamilton, Ont., who moderated the session where Dr. Goldenberg gave his report.
The study included 13,890 consecutive, prospectively enrolled patients who received a CIED during January 2015–April 2020 at any of five hospitals operated by either of two tertiary health care systems, one run by the University of Rochester and the second based at Sheba Medical Center in Tel HaShomer, Israel. The devices that made patients eligible for the study included permanent pacemakers, implantable cardioverter defibrillators, cardiac resynchronization therapy devices, and implantable cardiac monitors. A blinded adjudication committee composed of electrophysiologists identified the arrhythmic episodes.
At entry into the study (the time of device implantation), 12,992 patients were not receiving an SGLT2 inhibitor (94%) and 898 (6%) were receiving a drug from this class. Of those, 39% were on dapagliflozin (Farxiga), 35% were on empagliflozin (Jardiance), and 26% were on canagliflozin (Invokana).
Patients receiving an SGLT2 inhibitor at baseline were on average substantially younger than the patients not on this drug class (59 years vs. 69 years); they had a substantially higher prevalence of diabetes (78% vs. 25%), and ischemic cardiomyopathy (63% vs. 39%). Patients on an SGLT2 inhibitor at baseline also had more modestly higher prevalence rates of prior heart failure (38% vs. 31%), and hypertension (69% vs. 63%). Prevalence of a history of atrial fibrillation (AFib) was nearly the same in both groups: 31% in patients on an SGLT2 inhibitor and 35% in those not on these drugs.
The study’s primary endpoint was the total number of arrhythmia events during follow-up of 24,442 patient-years, during which patients exhibited 19,633 atrial arrhythmia events and 3,231 ventricular arrhythmia events.
1% absolute reduction in atrial arrhythmias
A multivariate analysis of the entire population – adjusted for baseline differences in age, diabetes, sex, and history of AFib – showed that treatment with an SGLT2 inhibitor at baseline was linked with a significant 24% relative reduction in incident atrial arrhythmia events, a significant 24% reduction in both atrial and ventricular arrhythmia events, and a 42% relative reduction in all-cause deaths, compared with no SGLT2-inhibitor treatment.
The only analyzed endpoint that showed no significant between-group difference was incidence of ventricular arrhythmias, which was a relative 7% lower in the SGLT2-inhibitor group.
On an absolute basis, treatment with an SGLT2 inhibitor was tied to about a 1% lower rate of atrial arrhythmia events per year, a reduction from a 2.5% rate in those not on an SGLT2 inhibitor to about a 1.5% rate in those taking this drug class.
A second, confirmatory analysis used propensity score matching to identify 5,323 patients not on an SGLT2 inhibitor at baseline who closely matched the 898 patients on an SGLT2 inhibitor. The multivariate modeling for this analysis also adjusted for age, diabetes, sex, and history of AFib.
The results of these analyses closely matched the calculations that used the entire study population. Relative to patients not on an SGLT2 inhibitor those on a drug from this class had 23% fewer atrial arrhythmias, 44% fewer total death, and 22% fewer atrial or ventricular arrhythmias, all significant differences. However, ventricular arrhythmias only reduced by a relative 5%, a nonsignificant difference.
In the propensity score–matched analysis, the absolute reduction in atrial arrhythmias in those on an SGLT2 inhibitor at baseline was roughly 1.3% fewer per year, compared with those not on this drug class.
The study was funded by an unrestricted grant to the University of Rochester from AstraZeneca, the company that markets the SGLT2 inhibitor dapagliflozin (Farxiga). Dr. Goldenberg and Dr. Van Spall had no disclosures.
FROM AHA 2021
Does vitamin D benefit only those who are deficient?
, suggests a new large-scale analysis.
Data on more than 380,000 participants gathered from 35 studies showed that, overall, there is no significant relationship between 25(OH)D concentrations, a clinical indicator of vitamin D status, and the incidence of coronary heart disease (CHD), stroke, or all-cause death, in a Mendelian randomization analysis.
However, Stephen Burgess, PhD, and colleagues showed that, in vitamin D–deficient individuals, each 10 nmol/L increase in 25(OH)D concentrations reduced the risk of all-cause mortality by 31%.
The research, published in The Lancet Diabetes & Endocrinology, also suggests there was a nonsignificant link between 25(OH)D concentrations and stroke and CHD, but again, only in vitamin D deficient individuals.
In an accompanying editorial, Guillaume Butler-Laporte, MD, and J. Brent Richards, MD, praise the researchers on their study methodology.
They add that the results “could have important public health and clinical consequences” and will “allow clinicians to better weigh the potential benefits of supplementation against its risk,” such as financial cost, “for better patient care – particularly among those with frank vitamin D deficiency.”
They continue: “Given that vitamin D deficiency is relatively common and vitamin D supplementation is safe, the rationale exists to test the effect of vitamin D supplementation in those with deficiency in large-scale randomized controlled trials.”
However, Dr. Butler-Laporte and Dr. Richards, of the Lady Davis Institute, Jewish General Hospital, Montreal, also note the study has several limitations, including the fact that the lifetime exposure to lower vitamin D levels captured by Mendelian randomization may result in larger effect sizes than in conventional trials.
Prior RCTS underpowered to detect effects of vitamin D supplements
“There are several potential mechanisms by which vitamin D could be protective for cardiovascular mortality, including mechanisms linking low vitamin D status with hyperparathyroidism and low serum calcium and phosphate,” write Dr. Burgess of the MRC Biostatistics Unit, University of Cambridge (England), and coauthors.
They also highlight that vitamin D is “further implicated in endothelial cell function” and affects the transcription of genes linked to cell division and apoptosis, providing “potential mechanisms implicating vitamin D for cancer.”
The researchers note that, while epidemiologic studies have “consistently” found a link between 25(OH)D levels and increased risk of cardiovascular disease, all-cause mortality, and other chronic diseases, several large trials of vitamin D supplementation have reported “null results.”
They argue, however, that many of these trials have recruited individuals “irrespective of baseline 25(OH)D concentration” and have been underpowered to detect the effects of supplementation.
To overcome these limitations, the team gathered data from the UK Biobank, the European Prospective Investigation Into Cancer and Nutrition Cardiovascular Disease (EPIC-CVD) study, 31 studies from the Vitamin D Studies Collaboration (VitDSC), and two Copenhagen population-based studies.
They first performed an observational study that included 384,721 individuals from the UK Biobank and 26,336 from EPIC-CVD who had a valid 25(OH)D measurement and no previously known cardiovascular disease at baseline.
Researchers also included 67,992 participants from the VitDSC studies who did not have previously known cardiovascular disease. They analyzed 25(OH)D concentrations, conventional cardiovascular risk factors, and major incident cardiovascular morbidity and mortality using individual participant data.
The results showed that, at low 25(OH)D concentrations, there was an inverse association between 25(OH)D and incident CHD, stroke, and all-cause mortality.
Next, the team conducted a Mendelian randomization analysis on 333,002 individuals from the UK Biobank and 26,336 from EPIC-CVD who were of European ancestry and had both a valid 25(OH)D measurement and genetic data that passed quality-control steps.
Information on 31,362 participants in the Copenhagen population-based studies was also included, giving a total of 386,406 individuals, of whom 33,546 had CHD, 18,166 had a stroke, and 27,885 died.
The mean age of participants ranged from 54.8 to 57.5 years, and between 53.4% and 55.4% were female.
Up to 7% of study participants were vitamin D deficient
The 25(OH)D analysis indicated that 3.9% of UK Biobank and 3.7% of Copenhagen study participants were deficient, compared with 6.9% in EPIC-CVD.
Across the full range of 25(OH)D concentrations, there was no significant association between genetically predicted 25(OH)D levels and CHD, stroke, or all-cause mortality.
However, restricting the analysis to individuals deemed vitamin D deficient (25[OH]D concentration < 25 nmol/L) revealed there was “strong evidence” for an inverse association with all-cause mortality, at an odds ratio per 10 nmol/L increase in genetically predicted 25(OH)D concentration of 0.69 (P < .0001), the team notes.
There were also nonsignificant associations between being in the deficient stratum and CHD, at an odds ratio of 0.89 (P = .14), and stroke, at an odds ratio of 0.85 (P = .09).
Further analysis suggests the association between 25(OH)D concentrations and all-cause mortality has a “clear threshold shape,” the researchers say, with evidence of an inverse association at concentrations below 40 nmol/L and null associations above that threshold.
They acknowledge, however, that their study has several potential limitations, including the assumption in their Mendelian randomization that the “only causal pathway from the genetic variants to the outcome is via 25(OH)D concentrations.”
Moreover, the genetic variants may affect 25(OH)D concentrations in a different way from “dietary supplementation or other clinical interventions.”
They also concede that their study was limited to middle-aged participants of European ancestries, which means the findings “might not be applicable to other populations.”
The study was funded by the British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer. Dr. Burgess has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article first appeared on Medscape.com.
, suggests a new large-scale analysis.
Data on more than 380,000 participants gathered from 35 studies showed that, overall, there is no significant relationship between 25(OH)D concentrations, a clinical indicator of vitamin D status, and the incidence of coronary heart disease (CHD), stroke, or all-cause death, in a Mendelian randomization analysis.
However, Stephen Burgess, PhD, and colleagues showed that, in vitamin D–deficient individuals, each 10 nmol/L increase in 25(OH)D concentrations reduced the risk of all-cause mortality by 31%.
The research, published in The Lancet Diabetes & Endocrinology, also suggests there was a nonsignificant link between 25(OH)D concentrations and stroke and CHD, but again, only in vitamin D deficient individuals.
In an accompanying editorial, Guillaume Butler-Laporte, MD, and J. Brent Richards, MD, praise the researchers on their study methodology.
They add that the results “could have important public health and clinical consequences” and will “allow clinicians to better weigh the potential benefits of supplementation against its risk,” such as financial cost, “for better patient care – particularly among those with frank vitamin D deficiency.”
They continue: “Given that vitamin D deficiency is relatively common and vitamin D supplementation is safe, the rationale exists to test the effect of vitamin D supplementation in those with deficiency in large-scale randomized controlled trials.”
However, Dr. Butler-Laporte and Dr. Richards, of the Lady Davis Institute, Jewish General Hospital, Montreal, also note the study has several limitations, including the fact that the lifetime exposure to lower vitamin D levels captured by Mendelian randomization may result in larger effect sizes than in conventional trials.
Prior RCTS underpowered to detect effects of vitamin D supplements
“There are several potential mechanisms by which vitamin D could be protective for cardiovascular mortality, including mechanisms linking low vitamin D status with hyperparathyroidism and low serum calcium and phosphate,” write Dr. Burgess of the MRC Biostatistics Unit, University of Cambridge (England), and coauthors.
They also highlight that vitamin D is “further implicated in endothelial cell function” and affects the transcription of genes linked to cell division and apoptosis, providing “potential mechanisms implicating vitamin D for cancer.”
The researchers note that, while epidemiologic studies have “consistently” found a link between 25(OH)D levels and increased risk of cardiovascular disease, all-cause mortality, and other chronic diseases, several large trials of vitamin D supplementation have reported “null results.”
They argue, however, that many of these trials have recruited individuals “irrespective of baseline 25(OH)D concentration” and have been underpowered to detect the effects of supplementation.
To overcome these limitations, the team gathered data from the UK Biobank, the European Prospective Investigation Into Cancer and Nutrition Cardiovascular Disease (EPIC-CVD) study, 31 studies from the Vitamin D Studies Collaboration (VitDSC), and two Copenhagen population-based studies.
They first performed an observational study that included 384,721 individuals from the UK Biobank and 26,336 from EPIC-CVD who had a valid 25(OH)D measurement and no previously known cardiovascular disease at baseline.
Researchers also included 67,992 participants from the VitDSC studies who did not have previously known cardiovascular disease. They analyzed 25(OH)D concentrations, conventional cardiovascular risk factors, and major incident cardiovascular morbidity and mortality using individual participant data.
The results showed that, at low 25(OH)D concentrations, there was an inverse association between 25(OH)D and incident CHD, stroke, and all-cause mortality.
Next, the team conducted a Mendelian randomization analysis on 333,002 individuals from the UK Biobank and 26,336 from EPIC-CVD who were of European ancestry and had both a valid 25(OH)D measurement and genetic data that passed quality-control steps.
Information on 31,362 participants in the Copenhagen population-based studies was also included, giving a total of 386,406 individuals, of whom 33,546 had CHD, 18,166 had a stroke, and 27,885 died.
The mean age of participants ranged from 54.8 to 57.5 years, and between 53.4% and 55.4% were female.
Up to 7% of study participants were vitamin D deficient
The 25(OH)D analysis indicated that 3.9% of UK Biobank and 3.7% of Copenhagen study participants were deficient, compared with 6.9% in EPIC-CVD.
Across the full range of 25(OH)D concentrations, there was no significant association between genetically predicted 25(OH)D levels and CHD, stroke, or all-cause mortality.
However, restricting the analysis to individuals deemed vitamin D deficient (25[OH]D concentration < 25 nmol/L) revealed there was “strong evidence” for an inverse association with all-cause mortality, at an odds ratio per 10 nmol/L increase in genetically predicted 25(OH)D concentration of 0.69 (P < .0001), the team notes.
There were also nonsignificant associations between being in the deficient stratum and CHD, at an odds ratio of 0.89 (P = .14), and stroke, at an odds ratio of 0.85 (P = .09).
Further analysis suggests the association between 25(OH)D concentrations and all-cause mortality has a “clear threshold shape,” the researchers say, with evidence of an inverse association at concentrations below 40 nmol/L and null associations above that threshold.
They acknowledge, however, that their study has several potential limitations, including the assumption in their Mendelian randomization that the “only causal pathway from the genetic variants to the outcome is via 25(OH)D concentrations.”
Moreover, the genetic variants may affect 25(OH)D concentrations in a different way from “dietary supplementation or other clinical interventions.”
They also concede that their study was limited to middle-aged participants of European ancestries, which means the findings “might not be applicable to other populations.”
The study was funded by the British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer. Dr. Burgess has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article first appeared on Medscape.com.
, suggests a new large-scale analysis.
Data on more than 380,000 participants gathered from 35 studies showed that, overall, there is no significant relationship between 25(OH)D concentrations, a clinical indicator of vitamin D status, and the incidence of coronary heart disease (CHD), stroke, or all-cause death, in a Mendelian randomization analysis.
However, Stephen Burgess, PhD, and colleagues showed that, in vitamin D–deficient individuals, each 10 nmol/L increase in 25(OH)D concentrations reduced the risk of all-cause mortality by 31%.
The research, published in The Lancet Diabetes & Endocrinology, also suggests there was a nonsignificant link between 25(OH)D concentrations and stroke and CHD, but again, only in vitamin D deficient individuals.
In an accompanying editorial, Guillaume Butler-Laporte, MD, and J. Brent Richards, MD, praise the researchers on their study methodology.
They add that the results “could have important public health and clinical consequences” and will “allow clinicians to better weigh the potential benefits of supplementation against its risk,” such as financial cost, “for better patient care – particularly among those with frank vitamin D deficiency.”
They continue: “Given that vitamin D deficiency is relatively common and vitamin D supplementation is safe, the rationale exists to test the effect of vitamin D supplementation in those with deficiency in large-scale randomized controlled trials.”
However, Dr. Butler-Laporte and Dr. Richards, of the Lady Davis Institute, Jewish General Hospital, Montreal, also note the study has several limitations, including the fact that the lifetime exposure to lower vitamin D levels captured by Mendelian randomization may result in larger effect sizes than in conventional trials.
Prior RCTS underpowered to detect effects of vitamin D supplements
“There are several potential mechanisms by which vitamin D could be protective for cardiovascular mortality, including mechanisms linking low vitamin D status with hyperparathyroidism and low serum calcium and phosphate,” write Dr. Burgess of the MRC Biostatistics Unit, University of Cambridge (England), and coauthors.
They also highlight that vitamin D is “further implicated in endothelial cell function” and affects the transcription of genes linked to cell division and apoptosis, providing “potential mechanisms implicating vitamin D for cancer.”
The researchers note that, while epidemiologic studies have “consistently” found a link between 25(OH)D levels and increased risk of cardiovascular disease, all-cause mortality, and other chronic diseases, several large trials of vitamin D supplementation have reported “null results.”
They argue, however, that many of these trials have recruited individuals “irrespective of baseline 25(OH)D concentration” and have been underpowered to detect the effects of supplementation.
To overcome these limitations, the team gathered data from the UK Biobank, the European Prospective Investigation Into Cancer and Nutrition Cardiovascular Disease (EPIC-CVD) study, 31 studies from the Vitamin D Studies Collaboration (VitDSC), and two Copenhagen population-based studies.
They first performed an observational study that included 384,721 individuals from the UK Biobank and 26,336 from EPIC-CVD who had a valid 25(OH)D measurement and no previously known cardiovascular disease at baseline.
Researchers also included 67,992 participants from the VitDSC studies who did not have previously known cardiovascular disease. They analyzed 25(OH)D concentrations, conventional cardiovascular risk factors, and major incident cardiovascular morbidity and mortality using individual participant data.
The results showed that, at low 25(OH)D concentrations, there was an inverse association between 25(OH)D and incident CHD, stroke, and all-cause mortality.
Next, the team conducted a Mendelian randomization analysis on 333,002 individuals from the UK Biobank and 26,336 from EPIC-CVD who were of European ancestry and had both a valid 25(OH)D measurement and genetic data that passed quality-control steps.
Information on 31,362 participants in the Copenhagen population-based studies was also included, giving a total of 386,406 individuals, of whom 33,546 had CHD, 18,166 had a stroke, and 27,885 died.
The mean age of participants ranged from 54.8 to 57.5 years, and between 53.4% and 55.4% were female.
Up to 7% of study participants were vitamin D deficient
The 25(OH)D analysis indicated that 3.9% of UK Biobank and 3.7% of Copenhagen study participants were deficient, compared with 6.9% in EPIC-CVD.
Across the full range of 25(OH)D concentrations, there was no significant association between genetically predicted 25(OH)D levels and CHD, stroke, or all-cause mortality.
However, restricting the analysis to individuals deemed vitamin D deficient (25[OH]D concentration < 25 nmol/L) revealed there was “strong evidence” for an inverse association with all-cause mortality, at an odds ratio per 10 nmol/L increase in genetically predicted 25(OH)D concentration of 0.69 (P < .0001), the team notes.
There were also nonsignificant associations between being in the deficient stratum and CHD, at an odds ratio of 0.89 (P = .14), and stroke, at an odds ratio of 0.85 (P = .09).
Further analysis suggests the association between 25(OH)D concentrations and all-cause mortality has a “clear threshold shape,” the researchers say, with evidence of an inverse association at concentrations below 40 nmol/L and null associations above that threshold.
They acknowledge, however, that their study has several potential limitations, including the assumption in their Mendelian randomization that the “only causal pathway from the genetic variants to the outcome is via 25(OH)D concentrations.”
Moreover, the genetic variants may affect 25(OH)D concentrations in a different way from “dietary supplementation or other clinical interventions.”
They also concede that their study was limited to middle-aged participants of European ancestries, which means the findings “might not be applicable to other populations.”
The study was funded by the British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer. Dr. Burgess has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article first appeared on Medscape.com.
Empagliflozin a winner in challenging arena of stabilized acute HF
The sodium-glucose transporter 2 inhibitors, relative newcomers among first-line agents for chronic heart failure (HF), could well attain the same go-to status in patients hospitalized with acute HF if the EMPULSE trial has anything to say about it.
Of the study’s 530 such patients, those started on daily empagliflozin (Jardiance) soon after they were stabilized, compared with a control group, were less likely to die or be rehospitalized for HF over the next 3 months.
Also, “we saw an improvement in quality of life, we saw a greater reduction in body weight, and we didn’t see any safety concerns in this very vulnerable and sick patient population,” Adriaan A. Voors, MD, University Medical Center Groningen (the Netherlands), said when presenting the trial at the American Heart Association scientific sessions.
Patients assigned to empagliflozin had a 36% greater likelihood of showing a benefit as reflected in the treatment’s win ratio when opposed by placebo, an emerging way to express outcomes in cardiovascular clinical trials. The SGLT2 inhibitor’s win ratio for the primary endpoint was 1.36 (95% confidence interval, 1.09-1.68, P = .0054), Dr. Voors reported. The outcome consisted of death, number of HF events, time to first HF event, and 90-day change in quality of life scores.
There is reluctance in practice to start patients that early after decompensation on drugs used in chronic HF, Dr. Voors said in an interview. Empagliflozin in the trial was initiated in the stabilized setting an average of 3 days after hospital admission, he said. The trial should reassure physicians that the drug “is not only safe to start early in hospital, but it’s also beneficial to start early in hospital.”
EMPULSE, combined with support from other recent trials, “should be clinical practice changing, with early in-hospital initiation of SGLT2 inhibitors in patients hospitalized with HF being the expectation, along with clear recognition that delaying SGLT2 inhibitor initiation may expose patients to unnecessary harms and delays in improved health status,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, told this news organization.
“For patients with HF, irrespective of ejection fraction, early in-hospital initiation of SGLT2 inhibitors – once stabilized and in the absence of contraindications – should be considered a new standard of care,” said Fonarow, who was not part of EMPULSE.
The trial also lends new weight to the strategy of “simultaneous or rapid-sequence initiation” of the so-called four pillars of guideline-directed medical therapy of HF with reduced ejection fraction in patients hospitalized with HFrEF, once they are stabilized, Dr. Fonarow said. The four-pronged approach, he noted, consists of sacubitril/valsartan (Entresto), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor.
Indeed, the new findings “fill an important gap and are clearly practice changing,” agreed Nancy K. Sweitzer, MD, PhD, University of Arizona Sarver Heart Center, Tucson, as an invited discussant following Dr. Voors’ presentation. “Few therapies have been shown to impact the course of those hospitalized with acute decompensated heart failure.”
Of note in the trial, Dr. Sweitzer continued, patients were started on empagliflozin regardless of any drug therapy they might already be on for chronic HF. “Because patients in the EMPULSE trial could be enrolled with a new diagnosis of heart failure, they were, by definition, not all on chronic guideline-directed heart failure therapy. Nevertheless, such patients benefited equally from the study intervention,” she said.
“This is crucial, as it tells us these drugs have immediate and important effects and should not be withheld while other drug classes are initiated and optimized.”
EMPULSE entered patients hospitalized for acute HF, which could be de novo or a decompensation of chronic HF, without regard to ejection fraction or whether they had diabetes, and who were clinically stable after at least one dose of loop diuretics. Their ejection fractions averaged 35% and exceeded 40% in about one-third of the total cohort.
At 90 days in the win ratio analysis, the 265 patients assigned to empagliflozin 10 mg once daily were the “winners”; that is, they were more likely to show a clinical benefit about 54% of the time in paired match-ups of patient outcomes, compared with about 40% for the 265 in the control group. The match-ups were a tie 6.4% of the time.
The empagliflozin group also benefited significantly for the endpoint of death from any cause or first HF event, with a hazard ratio of 0.65 (95% CI, 0.43-0.99; P = .042). They also were less likely to experience acute renal failure (7.7% vs. 12.1% for the control group) or serious adverse events (32.3% vs. 43.6%), Dr. Voors reported.
Tempting as it might be, the findings can’t necessarily be generalized to other SGLT2 inhibitors without an evidence base. But as Dr. Voors observed, several ongoing trials are exploring dapagliflozin (Farxiga) in a similar clinical setting.
They include DICTATE-AHF in patients with diabetes admitted with acute HF, and DAPA ACT HF-TIMI 68, which is entering patients stabilized during hospitalization with acute decompensated HFrEF. The trials are scheduled for completion in 2022 and 2023, respectively.
EMPULSE was supported by the Boehringer Ingelheim–Eli Lilly Diabetes Alliance. Dr. Voors disclosed research support and consulting for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novo Nordisk, Novartis, and Roche Diagnostics. Dr. Sweitzer disclosed honoraria from Acorda and Myokardia, and reported receiving research support from Novartis and Merck. Dr. Fonarow cited honoraria from Abbott, Amgen, Janssen, Medtronic, Bayer, Merck, AstraZeneca, Cytokinetics, and Novartis.
A version of this article first appeared on Medscape.com.
The sodium-glucose transporter 2 inhibitors, relative newcomers among first-line agents for chronic heart failure (HF), could well attain the same go-to status in patients hospitalized with acute HF if the EMPULSE trial has anything to say about it.
Of the study’s 530 such patients, those started on daily empagliflozin (Jardiance) soon after they were stabilized, compared with a control group, were less likely to die or be rehospitalized for HF over the next 3 months.
Also, “we saw an improvement in quality of life, we saw a greater reduction in body weight, and we didn’t see any safety concerns in this very vulnerable and sick patient population,” Adriaan A. Voors, MD, University Medical Center Groningen (the Netherlands), said when presenting the trial at the American Heart Association scientific sessions.
Patients assigned to empagliflozin had a 36% greater likelihood of showing a benefit as reflected in the treatment’s win ratio when opposed by placebo, an emerging way to express outcomes in cardiovascular clinical trials. The SGLT2 inhibitor’s win ratio for the primary endpoint was 1.36 (95% confidence interval, 1.09-1.68, P = .0054), Dr. Voors reported. The outcome consisted of death, number of HF events, time to first HF event, and 90-day change in quality of life scores.
There is reluctance in practice to start patients that early after decompensation on drugs used in chronic HF, Dr. Voors said in an interview. Empagliflozin in the trial was initiated in the stabilized setting an average of 3 days after hospital admission, he said. The trial should reassure physicians that the drug “is not only safe to start early in hospital, but it’s also beneficial to start early in hospital.”
EMPULSE, combined with support from other recent trials, “should be clinical practice changing, with early in-hospital initiation of SGLT2 inhibitors in patients hospitalized with HF being the expectation, along with clear recognition that delaying SGLT2 inhibitor initiation may expose patients to unnecessary harms and delays in improved health status,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, told this news organization.
“For patients with HF, irrespective of ejection fraction, early in-hospital initiation of SGLT2 inhibitors – once stabilized and in the absence of contraindications – should be considered a new standard of care,” said Fonarow, who was not part of EMPULSE.
The trial also lends new weight to the strategy of “simultaneous or rapid-sequence initiation” of the so-called four pillars of guideline-directed medical therapy of HF with reduced ejection fraction in patients hospitalized with HFrEF, once they are stabilized, Dr. Fonarow said. The four-pronged approach, he noted, consists of sacubitril/valsartan (Entresto), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor.
Indeed, the new findings “fill an important gap and are clearly practice changing,” agreed Nancy K. Sweitzer, MD, PhD, University of Arizona Sarver Heart Center, Tucson, as an invited discussant following Dr. Voors’ presentation. “Few therapies have been shown to impact the course of those hospitalized with acute decompensated heart failure.”
Of note in the trial, Dr. Sweitzer continued, patients were started on empagliflozin regardless of any drug therapy they might already be on for chronic HF. “Because patients in the EMPULSE trial could be enrolled with a new diagnosis of heart failure, they were, by definition, not all on chronic guideline-directed heart failure therapy. Nevertheless, such patients benefited equally from the study intervention,” she said.
“This is crucial, as it tells us these drugs have immediate and important effects and should not be withheld while other drug classes are initiated and optimized.”
EMPULSE entered patients hospitalized for acute HF, which could be de novo or a decompensation of chronic HF, without regard to ejection fraction or whether they had diabetes, and who were clinically stable after at least one dose of loop diuretics. Their ejection fractions averaged 35% and exceeded 40% in about one-third of the total cohort.
At 90 days in the win ratio analysis, the 265 patients assigned to empagliflozin 10 mg once daily were the “winners”; that is, they were more likely to show a clinical benefit about 54% of the time in paired match-ups of patient outcomes, compared with about 40% for the 265 in the control group. The match-ups were a tie 6.4% of the time.
The empagliflozin group also benefited significantly for the endpoint of death from any cause or first HF event, with a hazard ratio of 0.65 (95% CI, 0.43-0.99; P = .042). They also were less likely to experience acute renal failure (7.7% vs. 12.1% for the control group) or serious adverse events (32.3% vs. 43.6%), Dr. Voors reported.
Tempting as it might be, the findings can’t necessarily be generalized to other SGLT2 inhibitors without an evidence base. But as Dr. Voors observed, several ongoing trials are exploring dapagliflozin (Farxiga) in a similar clinical setting.
They include DICTATE-AHF in patients with diabetes admitted with acute HF, and DAPA ACT HF-TIMI 68, which is entering patients stabilized during hospitalization with acute decompensated HFrEF. The trials are scheduled for completion in 2022 and 2023, respectively.
EMPULSE was supported by the Boehringer Ingelheim–Eli Lilly Diabetes Alliance. Dr. Voors disclosed research support and consulting for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novo Nordisk, Novartis, and Roche Diagnostics. Dr. Sweitzer disclosed honoraria from Acorda and Myokardia, and reported receiving research support from Novartis and Merck. Dr. Fonarow cited honoraria from Abbott, Amgen, Janssen, Medtronic, Bayer, Merck, AstraZeneca, Cytokinetics, and Novartis.
A version of this article first appeared on Medscape.com.
The sodium-glucose transporter 2 inhibitors, relative newcomers among first-line agents for chronic heart failure (HF), could well attain the same go-to status in patients hospitalized with acute HF if the EMPULSE trial has anything to say about it.
Of the study’s 530 such patients, those started on daily empagliflozin (Jardiance) soon after they were stabilized, compared with a control group, were less likely to die or be rehospitalized for HF over the next 3 months.
Also, “we saw an improvement in quality of life, we saw a greater reduction in body weight, and we didn’t see any safety concerns in this very vulnerable and sick patient population,” Adriaan A. Voors, MD, University Medical Center Groningen (the Netherlands), said when presenting the trial at the American Heart Association scientific sessions.
Patients assigned to empagliflozin had a 36% greater likelihood of showing a benefit as reflected in the treatment’s win ratio when opposed by placebo, an emerging way to express outcomes in cardiovascular clinical trials. The SGLT2 inhibitor’s win ratio for the primary endpoint was 1.36 (95% confidence interval, 1.09-1.68, P = .0054), Dr. Voors reported. The outcome consisted of death, number of HF events, time to first HF event, and 90-day change in quality of life scores.
There is reluctance in practice to start patients that early after decompensation on drugs used in chronic HF, Dr. Voors said in an interview. Empagliflozin in the trial was initiated in the stabilized setting an average of 3 days after hospital admission, he said. The trial should reassure physicians that the drug “is not only safe to start early in hospital, but it’s also beneficial to start early in hospital.”
EMPULSE, combined with support from other recent trials, “should be clinical practice changing, with early in-hospital initiation of SGLT2 inhibitors in patients hospitalized with HF being the expectation, along with clear recognition that delaying SGLT2 inhibitor initiation may expose patients to unnecessary harms and delays in improved health status,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, told this news organization.
“For patients with HF, irrespective of ejection fraction, early in-hospital initiation of SGLT2 inhibitors – once stabilized and in the absence of contraindications – should be considered a new standard of care,” said Fonarow, who was not part of EMPULSE.
The trial also lends new weight to the strategy of “simultaneous or rapid-sequence initiation” of the so-called four pillars of guideline-directed medical therapy of HF with reduced ejection fraction in patients hospitalized with HFrEF, once they are stabilized, Dr. Fonarow said. The four-pronged approach, he noted, consists of sacubitril/valsartan (Entresto), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor.
Indeed, the new findings “fill an important gap and are clearly practice changing,” agreed Nancy K. Sweitzer, MD, PhD, University of Arizona Sarver Heart Center, Tucson, as an invited discussant following Dr. Voors’ presentation. “Few therapies have been shown to impact the course of those hospitalized with acute decompensated heart failure.”
Of note in the trial, Dr. Sweitzer continued, patients were started on empagliflozin regardless of any drug therapy they might already be on for chronic HF. “Because patients in the EMPULSE trial could be enrolled with a new diagnosis of heart failure, they were, by definition, not all on chronic guideline-directed heart failure therapy. Nevertheless, such patients benefited equally from the study intervention,” she said.
“This is crucial, as it tells us these drugs have immediate and important effects and should not be withheld while other drug classes are initiated and optimized.”
EMPULSE entered patients hospitalized for acute HF, which could be de novo or a decompensation of chronic HF, without regard to ejection fraction or whether they had diabetes, and who were clinically stable after at least one dose of loop diuretics. Their ejection fractions averaged 35% and exceeded 40% in about one-third of the total cohort.
At 90 days in the win ratio analysis, the 265 patients assigned to empagliflozin 10 mg once daily were the “winners”; that is, they were more likely to show a clinical benefit about 54% of the time in paired match-ups of patient outcomes, compared with about 40% for the 265 in the control group. The match-ups were a tie 6.4% of the time.
The empagliflozin group also benefited significantly for the endpoint of death from any cause or first HF event, with a hazard ratio of 0.65 (95% CI, 0.43-0.99; P = .042). They also were less likely to experience acute renal failure (7.7% vs. 12.1% for the control group) or serious adverse events (32.3% vs. 43.6%), Dr. Voors reported.
Tempting as it might be, the findings can’t necessarily be generalized to other SGLT2 inhibitors without an evidence base. But as Dr. Voors observed, several ongoing trials are exploring dapagliflozin (Farxiga) in a similar clinical setting.
They include DICTATE-AHF in patients with diabetes admitted with acute HF, and DAPA ACT HF-TIMI 68, which is entering patients stabilized during hospitalization with acute decompensated HFrEF. The trials are scheduled for completion in 2022 and 2023, respectively.
EMPULSE was supported by the Boehringer Ingelheim–Eli Lilly Diabetes Alliance. Dr. Voors disclosed research support and consulting for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novo Nordisk, Novartis, and Roche Diagnostics. Dr. Sweitzer disclosed honoraria from Acorda and Myokardia, and reported receiving research support from Novartis and Merck. Dr. Fonarow cited honoraria from Abbott, Amgen, Janssen, Medtronic, Bayer, Merck, AstraZeneca, Cytokinetics, and Novartis.
A version of this article first appeared on Medscape.com.
FROM AHA 2021
EMPEROR-Preserved findings confirmed in ‘true’ HFpEF patients
Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).
The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.
Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.
“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.
Streamlining heart failure treatment
The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.
That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.
“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
Treatment prevents hospitalization for heart failure
The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.
The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.
“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
Further benefits in patients with an LVEF of at least 50%
Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:
- The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
- Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
- Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
- Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.
Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.
The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m2.
EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.
Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).
The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.
Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.
“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.
Streamlining heart failure treatment
The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.
That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.
“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
Treatment prevents hospitalization for heart failure
The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.
The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.
“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
Further benefits in patients with an LVEF of at least 50%
Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:
- The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
- Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
- Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
- Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.
Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.
The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m2.
EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.
Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).
The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.
Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.
“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.
Streamlining heart failure treatment
The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.
That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.
“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
Treatment prevents hospitalization for heart failure
The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.
The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.
“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
Further benefits in patients with an LVEF of at least 50%
Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:
- The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
- Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
- Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
- Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.
Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.
The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m2.
EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.
FROM AHA2021
Contact allergens in medical devices: A cause for concern?
Despite the clinical value of medical devices, there is a potential for these products to cause adverse skin reactions in some patients. highlighting the possibility of a high prevalence of contact allergens in these devices.
“We found it important to publish these findings, because up until now no clear figures have been reported regarding this particular clinical problem,” said study author Olivier Aerts, MD, a researcher in the contact allergy unit at the University Hospital Antwerp, Belgium, in an interview with this news organization.
For the study, Dr. Aerts and colleagues conducted a retrospective analysis of medical device users with suspected allergic contact dermatitis. All patients had been patch tested at a tertiary European clinic between 2018 and 2020.
The cohort included patients who experienced suspected contact allergy from medical adhesives (n = 57), gloves (n = 38), topical and surface medical devices (n = 38), glucose sensors and insulin pumps (n = 74), and prostheses (n = 75). Other medical products associated with contact allergy in another 44 patients included surgical glues, face masks, compression stockings, condoms, and suture materials.
Overall, 326 patients had been patch-tested during the 30-month study period. Approximately 25.8% of all patients – including 299 adults and 27 children – were referred for contact allergy associated with medical devices.
Acrylates were the most frequently encountered contact allergens and were found in diabetes devices and medical adhesives. Potential skin sensitizers included colophonium-related substances, D-limonene, isothiazolinone derivatives, salicylates, and sulphites, all of which were identified across most products.
According to the investigators, many of the labels for the medical devices made no mention of the potential skin sensitizers, except in the cases of some topical and surface disinfectants. And many topical products are often marketed as medical devices rather than cosmetics, further complicating labeling issues, according to Dr. Aerts.
“What should be done to help any patient suffering from allergic contact due to medical devices is that these devices should be labeled with all their components, or at the very least with the potential skin sensitizers these may contain,” Dr. Aerts explained. He added that manufacturers should “establish more cooperation with physicians/dermatologists who evaluate such patients,” a cooperation that often exists with cosmetic companies.
Dr. Aerts noted that while it’s important for patch testers and dermatologists to be aware of the prevalence of allergic contact dermatitis in medical device users, companies producing these devices should also be aware of these potential issues. “Additionally, legislators/regulators should perhaps focus some more on the cutaneous side effects these products may provoke,” he said, “as this awareness may hopefully also serve as a stimulant to perform more clinical allergy research in this field.”
Leonard Bielory, MD, an allergist at Robert Wood Johnson University Hospital in Rahway, New Jersey, told this news organization that the findings are “alarming” and should heighten clinicians’ awareness of the possibility of allergic contact dermatitis among medical device users.
Dr. Bielory, who wasn’t involved in the research, noted that the findings from this study may not be entirely generalizable to the U.S., given the study was performed in Europe. “In contrast to other countries, the U.S. is very conscientious about allergic responses to items being used in hospitals,” he added, “or such that the issue here is that many of these things would be an adverse reaction, which you have to report.” He suggested that further research in this field is needed to determine the prevalence of possible skin sensitizers in products specifically developed and marketed in the U.S.
The study had no specific funding. Dr. Aerts and Dr. Bielory have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Despite the clinical value of medical devices, there is a potential for these products to cause adverse skin reactions in some patients. highlighting the possibility of a high prevalence of contact allergens in these devices.
“We found it important to publish these findings, because up until now no clear figures have been reported regarding this particular clinical problem,” said study author Olivier Aerts, MD, a researcher in the contact allergy unit at the University Hospital Antwerp, Belgium, in an interview with this news organization.
For the study, Dr. Aerts and colleagues conducted a retrospective analysis of medical device users with suspected allergic contact dermatitis. All patients had been patch tested at a tertiary European clinic between 2018 and 2020.
The cohort included patients who experienced suspected contact allergy from medical adhesives (n = 57), gloves (n = 38), topical and surface medical devices (n = 38), glucose sensors and insulin pumps (n = 74), and prostheses (n = 75). Other medical products associated with contact allergy in another 44 patients included surgical glues, face masks, compression stockings, condoms, and suture materials.
Overall, 326 patients had been patch-tested during the 30-month study period. Approximately 25.8% of all patients – including 299 adults and 27 children – were referred for contact allergy associated with medical devices.
Acrylates were the most frequently encountered contact allergens and were found in diabetes devices and medical adhesives. Potential skin sensitizers included colophonium-related substances, D-limonene, isothiazolinone derivatives, salicylates, and sulphites, all of which were identified across most products.
According to the investigators, many of the labels for the medical devices made no mention of the potential skin sensitizers, except in the cases of some topical and surface disinfectants. And many topical products are often marketed as medical devices rather than cosmetics, further complicating labeling issues, according to Dr. Aerts.
“What should be done to help any patient suffering from allergic contact due to medical devices is that these devices should be labeled with all their components, or at the very least with the potential skin sensitizers these may contain,” Dr. Aerts explained. He added that manufacturers should “establish more cooperation with physicians/dermatologists who evaluate such patients,” a cooperation that often exists with cosmetic companies.
Dr. Aerts noted that while it’s important for patch testers and dermatologists to be aware of the prevalence of allergic contact dermatitis in medical device users, companies producing these devices should also be aware of these potential issues. “Additionally, legislators/regulators should perhaps focus some more on the cutaneous side effects these products may provoke,” he said, “as this awareness may hopefully also serve as a stimulant to perform more clinical allergy research in this field.”
Leonard Bielory, MD, an allergist at Robert Wood Johnson University Hospital in Rahway, New Jersey, told this news organization that the findings are “alarming” and should heighten clinicians’ awareness of the possibility of allergic contact dermatitis among medical device users.
Dr. Bielory, who wasn’t involved in the research, noted that the findings from this study may not be entirely generalizable to the U.S., given the study was performed in Europe. “In contrast to other countries, the U.S. is very conscientious about allergic responses to items being used in hospitals,” he added, “or such that the issue here is that many of these things would be an adverse reaction, which you have to report.” He suggested that further research in this field is needed to determine the prevalence of possible skin sensitizers in products specifically developed and marketed in the U.S.
The study had no specific funding. Dr. Aerts and Dr. Bielory have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Despite the clinical value of medical devices, there is a potential for these products to cause adverse skin reactions in some patients. highlighting the possibility of a high prevalence of contact allergens in these devices.
“We found it important to publish these findings, because up until now no clear figures have been reported regarding this particular clinical problem,” said study author Olivier Aerts, MD, a researcher in the contact allergy unit at the University Hospital Antwerp, Belgium, in an interview with this news organization.
For the study, Dr. Aerts and colleagues conducted a retrospective analysis of medical device users with suspected allergic contact dermatitis. All patients had been patch tested at a tertiary European clinic between 2018 and 2020.
The cohort included patients who experienced suspected contact allergy from medical adhesives (n = 57), gloves (n = 38), topical and surface medical devices (n = 38), glucose sensors and insulin pumps (n = 74), and prostheses (n = 75). Other medical products associated with contact allergy in another 44 patients included surgical glues, face masks, compression stockings, condoms, and suture materials.
Overall, 326 patients had been patch-tested during the 30-month study period. Approximately 25.8% of all patients – including 299 adults and 27 children – were referred for contact allergy associated with medical devices.
Acrylates were the most frequently encountered contact allergens and were found in diabetes devices and medical adhesives. Potential skin sensitizers included colophonium-related substances, D-limonene, isothiazolinone derivatives, salicylates, and sulphites, all of which were identified across most products.
According to the investigators, many of the labels for the medical devices made no mention of the potential skin sensitizers, except in the cases of some topical and surface disinfectants. And many topical products are often marketed as medical devices rather than cosmetics, further complicating labeling issues, according to Dr. Aerts.
“What should be done to help any patient suffering from allergic contact due to medical devices is that these devices should be labeled with all their components, or at the very least with the potential skin sensitizers these may contain,” Dr. Aerts explained. He added that manufacturers should “establish more cooperation with physicians/dermatologists who evaluate such patients,” a cooperation that often exists with cosmetic companies.
Dr. Aerts noted that while it’s important for patch testers and dermatologists to be aware of the prevalence of allergic contact dermatitis in medical device users, companies producing these devices should also be aware of these potential issues. “Additionally, legislators/regulators should perhaps focus some more on the cutaneous side effects these products may provoke,” he said, “as this awareness may hopefully also serve as a stimulant to perform more clinical allergy research in this field.”
Leonard Bielory, MD, an allergist at Robert Wood Johnson University Hospital in Rahway, New Jersey, told this news organization that the findings are “alarming” and should heighten clinicians’ awareness of the possibility of allergic contact dermatitis among medical device users.
Dr. Bielory, who wasn’t involved in the research, noted that the findings from this study may not be entirely generalizable to the U.S., given the study was performed in Europe. “In contrast to other countries, the U.S. is very conscientious about allergic responses to items being used in hospitals,” he added, “or such that the issue here is that many of these things would be an adverse reaction, which you have to report.” He suggested that further research in this field is needed to determine the prevalence of possible skin sensitizers in products specifically developed and marketed in the U.S.
The study had no specific funding. Dr. Aerts and Dr. Bielory have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.