Diabetes

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

Sara Freeman/MDedge News

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

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

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

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

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

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

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

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

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

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

Dapagliflozin risks and benefits in advanced CKD

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sara Freeman/MDedge News

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

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

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

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

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

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

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

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

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

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

Dapagliflozin risks and benefits in advanced CKD

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sara Freeman/MDedge News

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

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

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

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

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

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

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

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

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

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

Dapagliflozin risks and benefits in advanced CKD

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Better outcomes, less anxiety for patients

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

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

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

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

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

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

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

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

Potential for harm?

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

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

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

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

State and federal efforts to curb prior authorization

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

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

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

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

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

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

With additional reporting by staff from this news organization.

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

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

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

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

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

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

Better outcomes, less anxiety for patients

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

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

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

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

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

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

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

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

Potential for harm?

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

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

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

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

State and federal efforts to curb prior authorization

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

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

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

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

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

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

With additional reporting by staff from this news organization.

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

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

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

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

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

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

Better outcomes, less anxiety for patients

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

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

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

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

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

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

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

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

Potential for harm?

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

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

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

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

State and federal efforts to curb prior authorization

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

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

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

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

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

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

With additional reporting by staff from this news organization.

The Food and Drug Administration has approved exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for use in children with type 2 diabetes down to 10 years of age, the agency announced July 22.

Olivier Le Moal/Getty Images

Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.

The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.

Exenatide extended release is not recommended as first-line treatment following diet and exercise.

The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.

Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.

Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.

But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.

The Food and Drug Administration has approved exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for use in children with type 2 diabetes down to 10 years of age, the agency announced July 22.

Olivier Le Moal/Getty Images

Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.

The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.

Exenatide extended release is not recommended as first-line treatment following diet and exercise.

The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.

Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.

Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.

But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.

The Food and Drug Administration has approved exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for use in children with type 2 diabetes down to 10 years of age, the agency announced July 22.

Olivier Le Moal/Getty Images

Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.

The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.

Exenatide extended release is not recommended as first-line treatment following diet and exercise.

The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.

Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.

Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.

But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.

“Purported” weight-loss products –12 dietary supplements and 2 alternative therapies – lack high-quality evidence to back up claims of efficacy, a systematic review by the Obesity Society reports.

Sally Kubetin/MDedge News

Most of the more than 300 published randomized controlled trials in the review were small and short, and only 0.5% found a statistically significant weight loss of up to 5 kg, John A. Batsis, MD, from the University of North Carolina at Chapel Hill, and colleagues reported in the journal Obesity.

“Despite the poor quality of these studies with high degrees of bias, most still failed to show efficacy of the product they were testing,” Srividya Kidambi, MD, from the Medical College of Wisconsin, Milwaukee, and colleagues from the Obesity Society’s Clinical Committee pointed out in an accompanying commentary.

“Yet these are the studies that are often used to support manufacturers’ claims of ‘clinically proven’ in their marketing,” they noted.

Most consumers, they continued, are unaware that these nondrug weight-loss products are not regulated by the Food and Drug Administration, but rather, if their ingredients are “generally regarded as safe,” they are treated as dietary supplements and require little or no testing to show either efficacy or safety.

“Our patients need to become aware that dietary supplements for weight loss are nothing more than a pipe dream, and as clinicians we would do well to talk with our patients and help steer them toward science-based treatments rather than the ‘Wild West’ of dietary supplements that are marketed for weight loss,” Scott Kahan, MD, MPH, coauthor of the review and commentary, told this news organization.

The dietary supplement industry has a strong lobby against legislation for more rigorous requirements for claims, noted Dr. Kahan, of the National Center for Weight and Wellness as well as George Washington University, Washington.

However, “there has to be some level of protection for consumers” who are faced with ads by “healthy skinny people saying this [product] can change your life.”

Clinical providers need to guide patients to “evidence-based interventions to support weight loss such as behavioral weight-loss interventions, [FDA-approved] medications, or bariatric surgery,” said Dr. Batsis, who also coauthored the commentary.

There is a “critical need” for more rigorous trials, and a partnership between researchers, funders, and industry, he added.

According to Dr. Kidambi and colleagues, “the use of these products will continue as long as they are allowed to be marketed with the aforementioned limited federal oversight and there is a lack of access to evidence-based obesity treatments.”

The commentary authors “call on regulatory authorities to critically examine the dietary supplement industry, including their role in promoting misleading claims and marketing products that have the potential to harm patients.”

They also urged public and private health insurance plans to “provide adequate resources for obesity management.”

And clinicians should “consider the lack of evidence for non–FDA-approved dietary supplements and therapies and guide their patients toward tested weight-management approaches.”
 

Subpar evidence, booming industry

“Annual sales of dietary supplements for weight loss are booming with an industry valued at $30 billion worldwide, despite subpar evidence” of efficacy, the commentary authors wrote by way of background.

After the Dietary Supplement Health and Education Act of 1994, the National Institutes of Health’s Office of Dietary Supplements was established “to strengthen the knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, and educating the public,” they explained.

However, dietary supplements and alternative therapies are endorsed by influencers and celebrities and marketed as a panacea for obesity and weight gain.
 

Literature review finds scant evidence

Consumers may believe that the “clinically proven” claims of efficacy of these “natural” weight-loss treatments have been thoroughly evaluated for safety and efficacy by the FDA, and clinicians lack information to counsel patients about this.

Therefore, although the Office of Dietary Supplements’ work has importantly advanced the science, the review authors wrote, members of the Obesity Society believed it was important to evaluate and perform a qualitative synthesis of the evidence for efficacy of non–FDA-regulated weight-loss supplements and alternative therapies to better inform clinicians and consumers.

From more than 20,000 citations of 53 dietary supplements and alternative therapies promoted for weight loss, the researchers identified 314 randomized controlled trials of 14 products that each had at least 5 randomized controlled trials.

The two types of alternative therapies in the review were mind-body interventions – which included behavioral therapies (for example, mindfulness and stress management), hypnosis, meditation, or massage – and acupuncture.

Several popular and widely used products (for example, human chorionic gonadotropin, raspberry ketones, nicotinamide adenine dinucleotide, vitamin infusions) did not meet the predefined number of published randomized controlled trials to be eligible for inclusion in the review.

The greatest number of trials were for acupuncture (45 trials), green tea (38), conjugated linoleic acid (31), ephedra with or without caffeine (31), mind-body therapies (22), and calcium and vitamin D (22). There were fewer trials of garcinia and/or hydroxycitrate (15), chitosan (9), phaseolus (7), pyruvate (7), chocolate/cocoa (6), chromium (6), guar gum (5), and phenylpropylamine (5).

Of the 314 studies, only 52 studies (16.5%) demonstrated that the products were efficacious and low risk, and only 16 studies (0.5%) reported a statistically significant between-group weight loss (0.3-4.93 kg).

For more information, in addition to their review and commentary, the authors refer clinicians to a dietary supplement label database.

The study was supported in part by grants from the National Institute on Aging. Dr. Batsis reported equity in SynchroHealth. Dr. Kidambi reported being the medical director for TOPS Center for Metabolic Health at the Medical College of Wisconsin, which is supported by TOPS. Dr. Kahan reported serving as a consultant for Novo Nordisk, Vivus, Gelesis, and Pfizer.

“Purported” weight-loss products –12 dietary supplements and 2 alternative therapies – lack high-quality evidence to back up claims of efficacy, a systematic review by the Obesity Society reports.

Sally Kubetin/MDedge News

Most of the more than 300 published randomized controlled trials in the review were small and short, and only 0.5% found a statistically significant weight loss of up to 5 kg, John A. Batsis, MD, from the University of North Carolina at Chapel Hill, and colleagues reported in the journal Obesity.

“Despite the poor quality of these studies with high degrees of bias, most still failed to show efficacy of the product they were testing,” Srividya Kidambi, MD, from the Medical College of Wisconsin, Milwaukee, and colleagues from the Obesity Society’s Clinical Committee pointed out in an accompanying commentary.

“Yet these are the studies that are often used to support manufacturers’ claims of ‘clinically proven’ in their marketing,” they noted.

Most consumers, they continued, are unaware that these nondrug weight-loss products are not regulated by the Food and Drug Administration, but rather, if their ingredients are “generally regarded as safe,” they are treated as dietary supplements and require little or no testing to show either efficacy or safety.

“Our patients need to become aware that dietary supplements for weight loss are nothing more than a pipe dream, and as clinicians we would do well to talk with our patients and help steer them toward science-based treatments rather than the ‘Wild West’ of dietary supplements that are marketed for weight loss,” Scott Kahan, MD, MPH, coauthor of the review and commentary, told this news organization.

The dietary supplement industry has a strong lobby against legislation for more rigorous requirements for claims, noted Dr. Kahan, of the National Center for Weight and Wellness as well as George Washington University, Washington.

However, “there has to be some level of protection for consumers” who are faced with ads by “healthy skinny people saying this [product] can change your life.”

Clinical providers need to guide patients to “evidence-based interventions to support weight loss such as behavioral weight-loss interventions, [FDA-approved] medications, or bariatric surgery,” said Dr. Batsis, who also coauthored the commentary.

There is a “critical need” for more rigorous trials, and a partnership between researchers, funders, and industry, he added.

According to Dr. Kidambi and colleagues, “the use of these products will continue as long as they are allowed to be marketed with the aforementioned limited federal oversight and there is a lack of access to evidence-based obesity treatments.”

The commentary authors “call on regulatory authorities to critically examine the dietary supplement industry, including their role in promoting misleading claims and marketing products that have the potential to harm patients.”

They also urged public and private health insurance plans to “provide adequate resources for obesity management.”

And clinicians should “consider the lack of evidence for non–FDA-approved dietary supplements and therapies and guide their patients toward tested weight-management approaches.”
 

Subpar evidence, booming industry

“Annual sales of dietary supplements for weight loss are booming with an industry valued at $30 billion worldwide, despite subpar evidence” of efficacy, the commentary authors wrote by way of background.

After the Dietary Supplement Health and Education Act of 1994, the National Institutes of Health’s Office of Dietary Supplements was established “to strengthen the knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, and educating the public,” they explained.

However, dietary supplements and alternative therapies are endorsed by influencers and celebrities and marketed as a panacea for obesity and weight gain.
 

Literature review finds scant evidence

Consumers may believe that the “clinically proven” claims of efficacy of these “natural” weight-loss treatments have been thoroughly evaluated for safety and efficacy by the FDA, and clinicians lack information to counsel patients about this.

Therefore, although the Office of Dietary Supplements’ work has importantly advanced the science, the review authors wrote, members of the Obesity Society believed it was important to evaluate and perform a qualitative synthesis of the evidence for efficacy of non–FDA-regulated weight-loss supplements and alternative therapies to better inform clinicians and consumers.

From more than 20,000 citations of 53 dietary supplements and alternative therapies promoted for weight loss, the researchers identified 314 randomized controlled trials of 14 products that each had at least 5 randomized controlled trials.

The two types of alternative therapies in the review were mind-body interventions – which included behavioral therapies (for example, mindfulness and stress management), hypnosis, meditation, or massage – and acupuncture.

Several popular and widely used products (for example, human chorionic gonadotropin, raspberry ketones, nicotinamide adenine dinucleotide, vitamin infusions) did not meet the predefined number of published randomized controlled trials to be eligible for inclusion in the review.

The greatest number of trials were for acupuncture (45 trials), green tea (38), conjugated linoleic acid (31), ephedra with or without caffeine (31), mind-body therapies (22), and calcium and vitamin D (22). There were fewer trials of garcinia and/or hydroxycitrate (15), chitosan (9), phaseolus (7), pyruvate (7), chocolate/cocoa (6), chromium (6), guar gum (5), and phenylpropylamine (5).

Of the 314 studies, only 52 studies (16.5%) demonstrated that the products were efficacious and low risk, and only 16 studies (0.5%) reported a statistically significant between-group weight loss (0.3-4.93 kg).

For more information, in addition to their review and commentary, the authors refer clinicians to a dietary supplement label database.

The study was supported in part by grants from the National Institute on Aging. Dr. Batsis reported equity in SynchroHealth. Dr. Kidambi reported being the medical director for TOPS Center for Metabolic Health at the Medical College of Wisconsin, which is supported by TOPS. Dr. Kahan reported serving as a consultant for Novo Nordisk, Vivus, Gelesis, and Pfizer.

“Purported” weight-loss products –12 dietary supplements and 2 alternative therapies – lack high-quality evidence to back up claims of efficacy, a systematic review by the Obesity Society reports.

Sally Kubetin/MDedge News

Most of the more than 300 published randomized controlled trials in the review were small and short, and only 0.5% found a statistically significant weight loss of up to 5 kg, John A. Batsis, MD, from the University of North Carolina at Chapel Hill, and colleagues reported in the journal Obesity.

“Despite the poor quality of these studies with high degrees of bias, most still failed to show efficacy of the product they were testing,” Srividya Kidambi, MD, from the Medical College of Wisconsin, Milwaukee, and colleagues from the Obesity Society’s Clinical Committee pointed out in an accompanying commentary.

“Yet these are the studies that are often used to support manufacturers’ claims of ‘clinically proven’ in their marketing,” they noted.

Most consumers, they continued, are unaware that these nondrug weight-loss products are not regulated by the Food and Drug Administration, but rather, if their ingredients are “generally regarded as safe,” they are treated as dietary supplements and require little or no testing to show either efficacy or safety.

“Our patients need to become aware that dietary supplements for weight loss are nothing more than a pipe dream, and as clinicians we would do well to talk with our patients and help steer them toward science-based treatments rather than the ‘Wild West’ of dietary supplements that are marketed for weight loss,” Scott Kahan, MD, MPH, coauthor of the review and commentary, told this news organization.

The dietary supplement industry has a strong lobby against legislation for more rigorous requirements for claims, noted Dr. Kahan, of the National Center for Weight and Wellness as well as George Washington University, Washington.

However, “there has to be some level of protection for consumers” who are faced with ads by “healthy skinny people saying this [product] can change your life.”

Clinical providers need to guide patients to “evidence-based interventions to support weight loss such as behavioral weight-loss interventions, [FDA-approved] medications, or bariatric surgery,” said Dr. Batsis, who also coauthored the commentary.

There is a “critical need” for more rigorous trials, and a partnership between researchers, funders, and industry, he added.

According to Dr. Kidambi and colleagues, “the use of these products will continue as long as they are allowed to be marketed with the aforementioned limited federal oversight and there is a lack of access to evidence-based obesity treatments.”

The commentary authors “call on regulatory authorities to critically examine the dietary supplement industry, including their role in promoting misleading claims and marketing products that have the potential to harm patients.”

They also urged public and private health insurance plans to “provide adequate resources for obesity management.”

And clinicians should “consider the lack of evidence for non–FDA-approved dietary supplements and therapies and guide their patients toward tested weight-management approaches.”
 

Subpar evidence, booming industry

“Annual sales of dietary supplements for weight loss are booming with an industry valued at $30 billion worldwide, despite subpar evidence” of efficacy, the commentary authors wrote by way of background.

After the Dietary Supplement Health and Education Act of 1994, the National Institutes of Health’s Office of Dietary Supplements was established “to strengthen the knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, and educating the public,” they explained.

However, dietary supplements and alternative therapies are endorsed by influencers and celebrities and marketed as a panacea for obesity and weight gain.
 

Literature review finds scant evidence

Consumers may believe that the “clinically proven” claims of efficacy of these “natural” weight-loss treatments have been thoroughly evaluated for safety and efficacy by the FDA, and clinicians lack information to counsel patients about this.

Therefore, although the Office of Dietary Supplements’ work has importantly advanced the science, the review authors wrote, members of the Obesity Society believed it was important to evaluate and perform a qualitative synthesis of the evidence for efficacy of non–FDA-regulated weight-loss supplements and alternative therapies to better inform clinicians and consumers.

From more than 20,000 citations of 53 dietary supplements and alternative therapies promoted for weight loss, the researchers identified 314 randomized controlled trials of 14 products that each had at least 5 randomized controlled trials.

The two types of alternative therapies in the review were mind-body interventions – which included behavioral therapies (for example, mindfulness and stress management), hypnosis, meditation, or massage – and acupuncture.

Several popular and widely used products (for example, human chorionic gonadotropin, raspberry ketones, nicotinamide adenine dinucleotide, vitamin infusions) did not meet the predefined number of published randomized controlled trials to be eligible for inclusion in the review.

The greatest number of trials were for acupuncture (45 trials), green tea (38), conjugated linoleic acid (31), ephedra with or without caffeine (31), mind-body therapies (22), and calcium and vitamin D (22). There were fewer trials of garcinia and/or hydroxycitrate (15), chitosan (9), phaseolus (7), pyruvate (7), chocolate/cocoa (6), chromium (6), guar gum (5), and phenylpropylamine (5).

Of the 314 studies, only 52 studies (16.5%) demonstrated that the products were efficacious and low risk, and only 16 studies (0.5%) reported a statistically significant between-group weight loss (0.3-4.93 kg).

For more information, in addition to their review and commentary, the authors refer clinicians to a dietary supplement label database.

The study was supported in part by grants from the National Institute on Aging. Dr. Batsis reported equity in SynchroHealth. Dr. Kidambi reported being the medical director for TOPS Center for Metabolic Health at the Medical College of Wisconsin, which is supported by TOPS. Dr. Kahan reported serving as a consultant for Novo Nordisk, Vivus, Gelesis, and Pfizer.

The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).

Olivier Le Moal/Getty Images

The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.

The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.

Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”

She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.

She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”

Both 6-and 12-month results show benefit

The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.

Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.

The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).

Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).

At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.

Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.

The patients will be followed for a total of 24 months.

Commercial launch of HFX in the United States will begin immediately, the company said.

Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.

The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).

Olivier Le Moal/Getty Images

The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.

The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.

Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”

She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.

She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”

Both 6-and 12-month results show benefit

The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.

Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.

The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).

Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).

At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.

Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.

The patients will be followed for a total of 24 months.

Commercial launch of HFX in the United States will begin immediately, the company said.

Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.

The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).

Olivier Le Moal/Getty Images

The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.

The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.

Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”

She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.

She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”

Both 6-and 12-month results show benefit

The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.

Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.

The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).

Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).

At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.

Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.

The patients will be followed for a total of 24 months.

Commercial launch of HFX in the United States will begin immediately, the company said.

Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.

In patients with intermediate risk of atherosclerotic cardiovascular disease along with risk-enhancing factors, coronary artery calcium scoring may help more precisely calculate their need for statin therapy.

Furthermore, when the need for statin treatment isn’t so clear and patients need additional risk assessment, the scoring can provide further information to personalize clinical decision making, according to a cross-sectional study of 1,688 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) published in JAMA Cardiology.

And regardless of coronary artery calcium (CAC), a low ankle brachial index (ABI) score is a marker for statin therapy, the study found.

The study looked at CAC scoring in the context of ABI and other risk-enhancing factors identified in the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines: a family history of premature atherosclerotic cardiovascular disease (ASCVD), lipid and inflammatory biomarkers, chronic kidney disease, chronic inflammatory conditions, premature menopause or preeclampsia, and South Asian ancestry.

Any number of these factors can indicate the need for statins in people with borderline or intermediate risk. The guidelines also call for selective use of CAC to aid the decision-making process for statin therapy when the risk for developing atherosclerosis isn’t so clear.

“The novel risk-enhancing factors are not perfect,” said lead author Jaideep Patel, MD, director of preventive cardiology at Johns Hopkins Heart Center at Greater Baltimore Medical Center. He noted that the 2018 dyslipidemia guidelines suggested the risk for cardiovascular events rises when new risk-enhancing factors emerge, and that it was difficult to predict the extent to which each enhancer could change the 10-year risk. 
 

Utility of CAC

“In this setting, the most significant finding that supports the utility of CAC scoring is when CAC is absent – a CAC of 0 – even in the setting of any of these enhancers, whether it be single or multiple, the 10-year risk remains extremely low – at the very least below the accepted threshold to initiate statin therapy,” Dr. Patel said.

That threshold is below the 7.5% 10-year ASCVD incidence rate. Over the 12-year mean study follow-up, the ASCVD incidence rate among patients with a CAC score of 0 for all risk-enhancing factors was 7.5 events per 1,000 person years, with one exception: ABI had an incidence rate of 10.4 events per 1,000 person years. “A low ABI score should trigger statin initiation irrespective of CAC score,” Dr. Patel said.

The study found a CAC score of 0 in 45.7% of those with one or two risk-enhancing factors versus 40.3% in those with three or more. “Across all the risk enhancers (except low ABI), the prevalence of CAC of 0 was greater than 50% in women; that is, enhancers overestimate risk,” Dr. Patel said. “The prevalence of CAC of 0 was approximately 40% across all risk enhancers; that is, enhancers overestimate risk.”

Dr. Patel said previous studies have suggested the risk of a major cardiovascular event was almost identical for statin and nonstatin users with a CAC score of 0. “If there is uncertainty about statin use after the physician-patient risk discussion,” he said, “CAC scoring may be helpful to guide the use of statin therapy.”

Senior author Mahmoud Al Rifai, MD, MPH, added: “For example, if CAC was absent, a statin could be deprescribed if there’s disutility on the part of the patient, with ongoing lifestyle and risk factor modification efforts.” Dr. Al Rifai is a cardiology fellow at Baylor College of Medicine, Houston.

Dr. Patel said: “Alternatively, if CAC was present, then it would be prudent to continue statin therapy.”

While South Asian ethnicity is a risk enhancing factor, the investigators acknowledged that MESA didn’t recruit this population group.
 

Study confirms guidelines

The study “supports the contention of the [AHA/ACC] guidelines that, in people who are in this intermediate risk range, there may be factors that either favor statin treatment or suggest that statin treatment could be deferred,” said Neil J. Stone, MD, of Northwestern University, Chicago, and author of the 2013 ASCVD risk calculator. “The guidelines pointed out that risk-enhancing factors may be associated with an increase in lifetime risk, not necessarily short term, and so could inform a more personalized risk discussion.”

The study findings validate the utility of CAC for guiding statin therapy, Dr. Stone said. “For those who have felt that a calcium score is not useful,” he said, “this is additional evidence to show that, in the context of making a decision in those at intermediate risk as proposed by the guidelines, a calcium score is indeed very useful.”

Dr. Stone added: “An important clinical point not mentioned by the authors is that, when the patient has a CAC score of 0 and risk factors, this may be exactly the time to be aggressive with lifestyle to prevent them from developing a positive CAC score and atherosclerosis, because once atherosclerosis is present, treatment may not restore the risk back to the original lower state.”

Dr. Patel, Dr. Al Rifai, and Dr. Stone have no relevant relationships to disclose. A number of study coauthors disclosed multiple financial relationships.

In patients with intermediate risk of atherosclerotic cardiovascular disease along with risk-enhancing factors, coronary artery calcium scoring may help more precisely calculate their need for statin therapy.

Furthermore, when the need for statin treatment isn’t so clear and patients need additional risk assessment, the scoring can provide further information to personalize clinical decision making, according to a cross-sectional study of 1,688 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) published in JAMA Cardiology.

And regardless of coronary artery calcium (CAC), a low ankle brachial index (ABI) score is a marker for statin therapy, the study found.

The study looked at CAC scoring in the context of ABI and other risk-enhancing factors identified in the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines: a family history of premature atherosclerotic cardiovascular disease (ASCVD), lipid and inflammatory biomarkers, chronic kidney disease, chronic inflammatory conditions, premature menopause or preeclampsia, and South Asian ancestry.

Any number of these factors can indicate the need for statins in people with borderline or intermediate risk. The guidelines also call for selective use of CAC to aid the decision-making process for statin therapy when the risk for developing atherosclerosis isn’t so clear.

“The novel risk-enhancing factors are not perfect,” said lead author Jaideep Patel, MD, director of preventive cardiology at Johns Hopkins Heart Center at Greater Baltimore Medical Center. He noted that the 2018 dyslipidemia guidelines suggested the risk for cardiovascular events rises when new risk-enhancing factors emerge, and that it was difficult to predict the extent to which each enhancer could change the 10-year risk. 
 

Utility of CAC

“In this setting, the most significant finding that supports the utility of CAC scoring is when CAC is absent – a CAC of 0 – even in the setting of any of these enhancers, whether it be single or multiple, the 10-year risk remains extremely low – at the very least below the accepted threshold to initiate statin therapy,” Dr. Patel said.

That threshold is below the 7.5% 10-year ASCVD incidence rate. Over the 12-year mean study follow-up, the ASCVD incidence rate among patients with a CAC score of 0 for all risk-enhancing factors was 7.5 events per 1,000 person years, with one exception: ABI had an incidence rate of 10.4 events per 1,000 person years. “A low ABI score should trigger statin initiation irrespective of CAC score,” Dr. Patel said.

The study found a CAC score of 0 in 45.7% of those with one or two risk-enhancing factors versus 40.3% in those with three or more. “Across all the risk enhancers (except low ABI), the prevalence of CAC of 0 was greater than 50% in women; that is, enhancers overestimate risk,” Dr. Patel said. “The prevalence of CAC of 0 was approximately 40% across all risk enhancers; that is, enhancers overestimate risk.”

Dr. Patel said previous studies have suggested the risk of a major cardiovascular event was almost identical for statin and nonstatin users with a CAC score of 0. “If there is uncertainty about statin use after the physician-patient risk discussion,” he said, “CAC scoring may be helpful to guide the use of statin therapy.”

Senior author Mahmoud Al Rifai, MD, MPH, added: “For example, if CAC was absent, a statin could be deprescribed if there’s disutility on the part of the patient, with ongoing lifestyle and risk factor modification efforts.” Dr. Al Rifai is a cardiology fellow at Baylor College of Medicine, Houston.

Dr. Patel said: “Alternatively, if CAC was present, then it would be prudent to continue statin therapy.”

While South Asian ethnicity is a risk enhancing factor, the investigators acknowledged that MESA didn’t recruit this population group.
 

Study confirms guidelines

The study “supports the contention of the [AHA/ACC] guidelines that, in people who are in this intermediate risk range, there may be factors that either favor statin treatment or suggest that statin treatment could be deferred,” said Neil J. Stone, MD, of Northwestern University, Chicago, and author of the 2013 ASCVD risk calculator. “The guidelines pointed out that risk-enhancing factors may be associated with an increase in lifetime risk, not necessarily short term, and so could inform a more personalized risk discussion.”

The study findings validate the utility of CAC for guiding statin therapy, Dr. Stone said. “For those who have felt that a calcium score is not useful,” he said, “this is additional evidence to show that, in the context of making a decision in those at intermediate risk as proposed by the guidelines, a calcium score is indeed very useful.”

Dr. Stone added: “An important clinical point not mentioned by the authors is that, when the patient has a CAC score of 0 and risk factors, this may be exactly the time to be aggressive with lifestyle to prevent them from developing a positive CAC score and atherosclerosis, because once atherosclerosis is present, treatment may not restore the risk back to the original lower state.”

Dr. Patel, Dr. Al Rifai, and Dr. Stone have no relevant relationships to disclose. A number of study coauthors disclosed multiple financial relationships.

In patients with intermediate risk of atherosclerotic cardiovascular disease along with risk-enhancing factors, coronary artery calcium scoring may help more precisely calculate their need for statin therapy.

Furthermore, when the need for statin treatment isn’t so clear and patients need additional risk assessment, the scoring can provide further information to personalize clinical decision making, according to a cross-sectional study of 1,688 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) published in JAMA Cardiology.

And regardless of coronary artery calcium (CAC), a low ankle brachial index (ABI) score is a marker for statin therapy, the study found.

The study looked at CAC scoring in the context of ABI and other risk-enhancing factors identified in the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines: a family history of premature atherosclerotic cardiovascular disease (ASCVD), lipid and inflammatory biomarkers, chronic kidney disease, chronic inflammatory conditions, premature menopause or preeclampsia, and South Asian ancestry.

Any number of these factors can indicate the need for statins in people with borderline or intermediate risk. The guidelines also call for selective use of CAC to aid the decision-making process for statin therapy when the risk for developing atherosclerosis isn’t so clear.

“The novel risk-enhancing factors are not perfect,” said lead author Jaideep Patel, MD, director of preventive cardiology at Johns Hopkins Heart Center at Greater Baltimore Medical Center. He noted that the 2018 dyslipidemia guidelines suggested the risk for cardiovascular events rises when new risk-enhancing factors emerge, and that it was difficult to predict the extent to which each enhancer could change the 10-year risk. 
 

Utility of CAC

“In this setting, the most significant finding that supports the utility of CAC scoring is when CAC is absent – a CAC of 0 – even in the setting of any of these enhancers, whether it be single or multiple, the 10-year risk remains extremely low – at the very least below the accepted threshold to initiate statin therapy,” Dr. Patel said.

That threshold is below the 7.5% 10-year ASCVD incidence rate. Over the 12-year mean study follow-up, the ASCVD incidence rate among patients with a CAC score of 0 for all risk-enhancing factors was 7.5 events per 1,000 person years, with one exception: ABI had an incidence rate of 10.4 events per 1,000 person years. “A low ABI score should trigger statin initiation irrespective of CAC score,” Dr. Patel said.

The study found a CAC score of 0 in 45.7% of those with one or two risk-enhancing factors versus 40.3% in those with three or more. “Across all the risk enhancers (except low ABI), the prevalence of CAC of 0 was greater than 50% in women; that is, enhancers overestimate risk,” Dr. Patel said. “The prevalence of CAC of 0 was approximately 40% across all risk enhancers; that is, enhancers overestimate risk.”

Dr. Patel said previous studies have suggested the risk of a major cardiovascular event was almost identical for statin and nonstatin users with a CAC score of 0. “If there is uncertainty about statin use after the physician-patient risk discussion,” he said, “CAC scoring may be helpful to guide the use of statin therapy.”

Senior author Mahmoud Al Rifai, MD, MPH, added: “For example, if CAC was absent, a statin could be deprescribed if there’s disutility on the part of the patient, with ongoing lifestyle and risk factor modification efforts.” Dr. Al Rifai is a cardiology fellow at Baylor College of Medicine, Houston.

Dr. Patel said: “Alternatively, if CAC was present, then it would be prudent to continue statin therapy.”

While South Asian ethnicity is a risk enhancing factor, the investigators acknowledged that MESA didn’t recruit this population group.
 

Study confirms guidelines

The study “supports the contention of the [AHA/ACC] guidelines that, in people who are in this intermediate risk range, there may be factors that either favor statin treatment or suggest that statin treatment could be deferred,” said Neil J. Stone, MD, of Northwestern University, Chicago, and author of the 2013 ASCVD risk calculator. “The guidelines pointed out that risk-enhancing factors may be associated with an increase in lifetime risk, not necessarily short term, and so could inform a more personalized risk discussion.”

The study findings validate the utility of CAC for guiding statin therapy, Dr. Stone said. “For those who have felt that a calcium score is not useful,” he said, “this is additional evidence to show that, in the context of making a decision in those at intermediate risk as proposed by the guidelines, a calcium score is indeed very useful.”

Dr. Stone added: “An important clinical point not mentioned by the authors is that, when the patient has a CAC score of 0 and risk factors, this may be exactly the time to be aggressive with lifestyle to prevent them from developing a positive CAC score and atherosclerosis, because once atherosclerosis is present, treatment may not restore the risk back to the original lower state.”

Dr. Patel, Dr. Al Rifai, and Dr. Stone have no relevant relationships to disclose. A number of study coauthors disclosed multiple financial relationships.

ILLUSTRATIVE CASE

A 64-year-old overweight White man with a history of hypertension, hyperlipidemia, and HF with an ejection fraction (EF) of 40% presents for primary care follow-up after a recent inpatient admission for worsened HF symptoms. At baseline, he is comfortable at rest but becomes dyspneic upon walking to another room within his home. He is already taking a mineralocorticoid receptor antagonist, a high-intensity statin, a beta-blocker, and an angiotensin-converting enzyme (ACE) inhibitor. What other medication should be considered to minimize his cardiovascular (CV)risk?

An estimated 1% to 2% of the world’s adult population has HF.² Although the exact prevalence is difficult to quantify due to variations in definitions and diagnostic methods, the American Heart Association (AHA) estimated that 6.2 million Americans had HF between 2013 and 2016.³ Prevalence increases with age, with an annual incidence of approximately 35 per 1000 by age 85.⁴ Due to the significant morbidity and mortality associated with HF, advancements in treatment are needed.

SGLT2 inhibitors work within the proximal tubule of the kidneys, resulting in increased glucose and sodium excretion with secondary osmotic diuresis and therefore a modest reduction in serum glucose.^1,2,5,6 SGLT2 inhibitors are classically prescribed for hyperglycemia treatment in type 2 diabetes. However, preliminary data suggest that this class of medication also positively impacts cardiac function. The diuresis and natriuresis effects of SGLT2 inhibitors appear to optimize cardiac output and subsequent oxygen consumption through a reduction of afterload and preload.^1,2,5,6 Further, SGLT2 inhibitors may decrease inflammatory pathways and lead to a secondary reduction of cardiac remodeling via a reduction and modulation of inflammatory pathways. This reduction and modulation may also be associated with a reduction in development, and possibly a reversal, of hypertrophic cardiomyopathy, cardiac fibrosis, and atherosclerosis.^5,6 Some of the previously reported adverse effects of SGLT2 inhibitors include urinary tract infection, acute kidney injury, lower extremity amputation, bone fracture, and diabetic ketoacidosis.²

In several studies of patients with type 2 diabetes, SGLT2 inhibitors have shown benefit in reducing CV disease–related death and hospitalization for HF.^1,2,5,6 A recent expert consensus from the American College of Cardiology (ACC) states that SGLT2 therapy should be considered for any patient with type 2 diabetes who also has established atherosclerotic CV disease, HF (a clinical syndrome as defined in ACC/AHA guidelines), or diabetic kidney disease, or who is at a high risk for atherosclerotic CV disease (ie, has signs of end-organ damage, such as left ventricular hypertrophy or retinopathy, or multiple risk factors such as advanced age, smoking, hypertension, and family history).^7,8

Dapagliflozin demonstrated decreased HF exacerbations and CV deaths, improved patient-reported HF symptoms, and lower allcause mortality in patients both with and without diabetes.

Additionally, a 2019 randomized controlled trial (RCT) by Nassif et al showed that, compared to placebo, dapagliflozin significantly improved both patient-reported HF symptoms and cardiac natriuretic peptide levels over 12 weeks in patients with and without diabetes.⁹ In September 2020, ­UpToDate added SGLT2 inhibitors as an option for patients with continued symptoms of HF despite use of appropriate primary agents and mineralocorticoid receptor antagonists, whether or not they have type 2 diabetes; this update was based on 2 studies, 1 of which is reviewed here.¹⁰

STUDY SUMMARY

Dapagliflozin demonstrated better CV outcomes than placebo

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study is an RCT that compared dapagliflozin to placebo among 4744 patients ages 18 years and older who had HF with an EF ≤ 40% and NYHA class II, III, or IV symptoms. The study included patients with (41.8%) and without diabetes. Most patients were male (76.2%-77%), White (70%), and European (44.7%-46.1%).

Patients were randomized to receive either dapagliflozin 10 mg/d or a matching placebo in addition to standard HF therapy (including an ACE inhibitor, angiotensin receptor blocker, or sacubitril-valsartan plus a beta-blocker unless contraindicated; mineralocorticoid antagonist use was encouraged). Follow-up occurred at 14 days, 60 days, 4 months, and then every 4 months, for an average of about 18 months. Patients with diabetes continued to use their glucose-lowering therapies, with dose adjustments, as needed.

Continue to: The primary outcome...

The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous HF therapy) or death from a CV cause. Secondary outcomes included a composite of hospitalization for HF or CV death; total number of hospitalizations for HF (including repeat admissions) and CV death; a change in Kansas City Cardiomyopathy Questionnaire symptom score; a composite of worsening renal function including a sustained (≥ 28 d) decline in the estimated glomerular filtration rate (eGFR) of ≥ 50%, end-stage renal disease (defined as sustained eGFR of < 15 mL/min/1.73 m², sustained dialysis, or renal transplantation), or renal death; and death from any cause.

The primary outcome of worsening HF or death from CV causes occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio [HR] = 0.74; 95% CI, 0.65-0.85; P < .001). The composite score of hospitalizations for HF plus death from a CV cause was lower in the dapagliflozin group compared to the placebo group (HR = 0.75; 95% CI, 0.65-0.85; P < .001).

Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications.

A total of 276 patients (11.6%) in the dapagliflozin group and 329 patients (13.9%) in the placebo group died from any cause (HR = 0.83; 95% CI, 0.71-0.97). More patients in the dapagliflozin group than in the placebo group had an improvement in symptom score (58.3% vs 50.9%; odds ratio = 1.15; 95% CI, 1.08-1.23; P < .001). Renal composite outcome did not differ between the 2 treatment groups. Potential adverse effects included volume depletion, renal adverse event, and major hypoglycemia, which occurred at the same rate in the treatment and placebo groups. There was no difference in outcomes or adverse effects between patients with and without diabetes.¹

WHAT'S NEW

Evidence supports dapagliflozin use in a new patient population

The DAPA-HF study compared dapagliflozin to placebo in HF patients both with and without diabetes and demonstrated decreased HF exacerbations and CV deaths, improved ­patient-reported HF symptoms, and lower all-cause mortality in the treatment group. This study supports use of dapagliflozin in a new patient population—those with HF—rather than solely in patients with diabetes, as the drug was originally marketed.

CAVEATS

Specific study population may limit generalizability

The DAPA-HF study included mostly male, White, European patients followed for an average of 18.2 months as part of initial Phase III studies funded by AstraZeneca (the pharmaceutical company that developed dapagliflozin). Given the potential conflict due to funding, all statistical results were verified by an independent academic group, and analyses were completed with an intention-to-treat model. The outlined benefits described here were only studied in a population of patients with reduced EF (≤ 40%), so the impact remains unclear for patients with preserved EF. Safety and benefits beyond 24 months were not studied in this RCT; therefore long-term data are still unknown.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Adding an SGLT2 inhibitor may be cost prohibitive for some patients

An SGLT2 inhibitor costs, on average, $500 to $600 for a 30-day supply, which may be prohibitive for some patients.¹¹ Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications, particularly glucose-lowering therapies, and the optimal prioritization of medications is not yet known.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 64-year-old overweight White man with a history of hypertension, hyperlipidemia, and HF with an ejection fraction (EF) of 40% presents for primary care follow-up after a recent inpatient admission for worsened HF symptoms. At baseline, he is comfortable at rest but becomes dyspneic upon walking to another room within his home. He is already taking a mineralocorticoid receptor antagonist, a high-intensity statin, a beta-blocker, and an angiotensin-converting enzyme (ACE) inhibitor. What other medication should be considered to minimize his cardiovascular (CV)risk?

An estimated 1% to 2% of the world’s adult population has HF.² Although the exact prevalence is difficult to quantify due to variations in definitions and diagnostic methods, the American Heart Association (AHA) estimated that 6.2 million Americans had HF between 2013 and 2016.³ Prevalence increases with age, with an annual incidence of approximately 35 per 1000 by age 85.⁴ Due to the significant morbidity and mortality associated with HF, advancements in treatment are needed.

SGLT2 inhibitors work within the proximal tubule of the kidneys, resulting in increased glucose and sodium excretion with secondary osmotic diuresis and therefore a modest reduction in serum glucose.^1,2,5,6 SGLT2 inhibitors are classically prescribed for hyperglycemia treatment in type 2 diabetes. However, preliminary data suggest that this class of medication also positively impacts cardiac function. The diuresis and natriuresis effects of SGLT2 inhibitors appear to optimize cardiac output and subsequent oxygen consumption through a reduction of afterload and preload.^1,2,5,6 Further, SGLT2 inhibitors may decrease inflammatory pathways and lead to a secondary reduction of cardiac remodeling via a reduction and modulation of inflammatory pathways. This reduction and modulation may also be associated with a reduction in development, and possibly a reversal, of hypertrophic cardiomyopathy, cardiac fibrosis, and atherosclerosis.^5,6 Some of the previously reported adverse effects of SGLT2 inhibitors include urinary tract infection, acute kidney injury, lower extremity amputation, bone fracture, and diabetic ketoacidosis.²

In several studies of patients with type 2 diabetes, SGLT2 inhibitors have shown benefit in reducing CV disease–related death and hospitalization for HF.^1,2,5,6 A recent expert consensus from the American College of Cardiology (ACC) states that SGLT2 therapy should be considered for any patient with type 2 diabetes who also has established atherosclerotic CV disease, HF (a clinical syndrome as defined in ACC/AHA guidelines), or diabetic kidney disease, or who is at a high risk for atherosclerotic CV disease (ie, has signs of end-organ damage, such as left ventricular hypertrophy or retinopathy, or multiple risk factors such as advanced age, smoking, hypertension, and family history).^7,8

Dapagliflozin demonstrated decreased HF exacerbations and CV deaths, improved patient-reported HF symptoms, and lower allcause mortality in patients both with and without diabetes.

Additionally, a 2019 randomized controlled trial (RCT) by Nassif et al showed that, compared to placebo, dapagliflozin significantly improved both patient-reported HF symptoms and cardiac natriuretic peptide levels over 12 weeks in patients with and without diabetes.⁹ In September 2020, ­UpToDate added SGLT2 inhibitors as an option for patients with continued symptoms of HF despite use of appropriate primary agents and mineralocorticoid receptor antagonists, whether or not they have type 2 diabetes; this update was based on 2 studies, 1 of which is reviewed here.¹⁰

STUDY SUMMARY

Dapagliflozin demonstrated better CV outcomes than placebo

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study is an RCT that compared dapagliflozin to placebo among 4744 patients ages 18 years and older who had HF with an EF ≤ 40% and NYHA class II, III, or IV symptoms. The study included patients with (41.8%) and without diabetes. Most patients were male (76.2%-77%), White (70%), and European (44.7%-46.1%).

Patients were randomized to receive either dapagliflozin 10 mg/d or a matching placebo in addition to standard HF therapy (including an ACE inhibitor, angiotensin receptor blocker, or sacubitril-valsartan plus a beta-blocker unless contraindicated; mineralocorticoid antagonist use was encouraged). Follow-up occurred at 14 days, 60 days, 4 months, and then every 4 months, for an average of about 18 months. Patients with diabetes continued to use their glucose-lowering therapies, with dose adjustments, as needed.

Continue to: The primary outcome...

The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous HF therapy) or death from a CV cause. Secondary outcomes included a composite of hospitalization for HF or CV death; total number of hospitalizations for HF (including repeat admissions) and CV death; a change in Kansas City Cardiomyopathy Questionnaire symptom score; a composite of worsening renal function including a sustained (≥ 28 d) decline in the estimated glomerular filtration rate (eGFR) of ≥ 50%, end-stage renal disease (defined as sustained eGFR of < 15 mL/min/1.73 m², sustained dialysis, or renal transplantation), or renal death; and death from any cause.

The primary outcome of worsening HF or death from CV causes occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio [HR] = 0.74; 95% CI, 0.65-0.85; P < .001). The composite score of hospitalizations for HF plus death from a CV cause was lower in the dapagliflozin group compared to the placebo group (HR = 0.75; 95% CI, 0.65-0.85; P < .001).

Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications.

A total of 276 patients (11.6%) in the dapagliflozin group and 329 patients (13.9%) in the placebo group died from any cause (HR = 0.83; 95% CI, 0.71-0.97). More patients in the dapagliflozin group than in the placebo group had an improvement in symptom score (58.3% vs 50.9%; odds ratio = 1.15; 95% CI, 1.08-1.23; P < .001). Renal composite outcome did not differ between the 2 treatment groups. Potential adverse effects included volume depletion, renal adverse event, and major hypoglycemia, which occurred at the same rate in the treatment and placebo groups. There was no difference in outcomes or adverse effects between patients with and without diabetes.¹

WHAT'S NEW

Evidence supports dapagliflozin use in a new patient population

The DAPA-HF study compared dapagliflozin to placebo in HF patients both with and without diabetes and demonstrated decreased HF exacerbations and CV deaths, improved ­patient-reported HF symptoms, and lower all-cause mortality in the treatment group. This study supports use of dapagliflozin in a new patient population—those with HF—rather than solely in patients with diabetes, as the drug was originally marketed.

CAVEATS

Specific study population may limit generalizability

The DAPA-HF study included mostly male, White, European patients followed for an average of 18.2 months as part of initial Phase III studies funded by AstraZeneca (the pharmaceutical company that developed dapagliflozin). Given the potential conflict due to funding, all statistical results were verified by an independent academic group, and analyses were completed with an intention-to-treat model. The outlined benefits described here were only studied in a population of patients with reduced EF (≤ 40%), so the impact remains unclear for patients with preserved EF. Safety and benefits beyond 24 months were not studied in this RCT; therefore long-term data are still unknown.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Adding an SGLT2 inhibitor may be cost prohibitive for some patients

An SGLT2 inhibitor costs, on average, $500 to $600 for a 30-day supply, which may be prohibitive for some patients.¹¹ Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications, particularly glucose-lowering therapies, and the optimal prioritization of medications is not yet known.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 64-year-old overweight White man with a history of hypertension, hyperlipidemia, and HF with an ejection fraction (EF) of 40% presents for primary care follow-up after a recent inpatient admission for worsened HF symptoms. At baseline, he is comfortable at rest but becomes dyspneic upon walking to another room within his home. He is already taking a mineralocorticoid receptor antagonist, a high-intensity statin, a beta-blocker, and an angiotensin-converting enzyme (ACE) inhibitor. What other medication should be considered to minimize his cardiovascular (CV)risk?

An estimated 1% to 2% of the world’s adult population has HF.² Although the exact prevalence is difficult to quantify due to variations in definitions and diagnostic methods, the American Heart Association (AHA) estimated that 6.2 million Americans had HF between 2013 and 2016.³ Prevalence increases with age, with an annual incidence of approximately 35 per 1000 by age 85.⁴ Due to the significant morbidity and mortality associated with HF, advancements in treatment are needed.

SGLT2 inhibitors work within the proximal tubule of the kidneys, resulting in increased glucose and sodium excretion with secondary osmotic diuresis and therefore a modest reduction in serum glucose.^1,2,5,6 SGLT2 inhibitors are classically prescribed for hyperglycemia treatment in type 2 diabetes. However, preliminary data suggest that this class of medication also positively impacts cardiac function. The diuresis and natriuresis effects of SGLT2 inhibitors appear to optimize cardiac output and subsequent oxygen consumption through a reduction of afterload and preload.^1,2,5,6 Further, SGLT2 inhibitors may decrease inflammatory pathways and lead to a secondary reduction of cardiac remodeling via a reduction and modulation of inflammatory pathways. This reduction and modulation may also be associated with a reduction in development, and possibly a reversal, of hypertrophic cardiomyopathy, cardiac fibrosis, and atherosclerosis.^5,6 Some of the previously reported adverse effects of SGLT2 inhibitors include urinary tract infection, acute kidney injury, lower extremity amputation, bone fracture, and diabetic ketoacidosis.²

In several studies of patients with type 2 diabetes, SGLT2 inhibitors have shown benefit in reducing CV disease–related death and hospitalization for HF.^1,2,5,6 A recent expert consensus from the American College of Cardiology (ACC) states that SGLT2 therapy should be considered for any patient with type 2 diabetes who also has established atherosclerotic CV disease, HF (a clinical syndrome as defined in ACC/AHA guidelines), or diabetic kidney disease, or who is at a high risk for atherosclerotic CV disease (ie, has signs of end-organ damage, such as left ventricular hypertrophy or retinopathy, or multiple risk factors such as advanced age, smoking, hypertension, and family history).^7,8

Dapagliflozin demonstrated decreased HF exacerbations and CV deaths, improved patient-reported HF symptoms, and lower allcause mortality in patients both with and without diabetes.

Additionally, a 2019 randomized controlled trial (RCT) by Nassif et al showed that, compared to placebo, dapagliflozin significantly improved both patient-reported HF symptoms and cardiac natriuretic peptide levels over 12 weeks in patients with and without diabetes.⁹ In September 2020, ­UpToDate added SGLT2 inhibitors as an option for patients with continued symptoms of HF despite use of appropriate primary agents and mineralocorticoid receptor antagonists, whether or not they have type 2 diabetes; this update was based on 2 studies, 1 of which is reviewed here.¹⁰

STUDY SUMMARY

Dapagliflozin demonstrated better CV outcomes than placebo

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study is an RCT that compared dapagliflozin to placebo among 4744 patients ages 18 years and older who had HF with an EF ≤ 40% and NYHA class II, III, or IV symptoms. The study included patients with (41.8%) and without diabetes. Most patients were male (76.2%-77%), White (70%), and European (44.7%-46.1%).

Patients were randomized to receive either dapagliflozin 10 mg/d or a matching placebo in addition to standard HF therapy (including an ACE inhibitor, angiotensin receptor blocker, or sacubitril-valsartan plus a beta-blocker unless contraindicated; mineralocorticoid antagonist use was encouraged). Follow-up occurred at 14 days, 60 days, 4 months, and then every 4 months, for an average of about 18 months. Patients with diabetes continued to use their glucose-lowering therapies, with dose adjustments, as needed.

Continue to: The primary outcome...

The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous HF therapy) or death from a CV cause. Secondary outcomes included a composite of hospitalization for HF or CV death; total number of hospitalizations for HF (including repeat admissions) and CV death; a change in Kansas City Cardiomyopathy Questionnaire symptom score; a composite of worsening renal function including a sustained (≥ 28 d) decline in the estimated glomerular filtration rate (eGFR) of ≥ 50%, end-stage renal disease (defined as sustained eGFR of < 15 mL/min/1.73 m², sustained dialysis, or renal transplantation), or renal death; and death from any cause.

The primary outcome of worsening HF or death from CV causes occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio [HR] = 0.74; 95% CI, 0.65-0.85; P < .001). The composite score of hospitalizations for HF plus death from a CV cause was lower in the dapagliflozin group compared to the placebo group (HR = 0.75; 95% CI, 0.65-0.85; P < .001).

Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications.

A total of 276 patients (11.6%) in the dapagliflozin group and 329 patients (13.9%) in the placebo group died from any cause (HR = 0.83; 95% CI, 0.71-0.97). More patients in the dapagliflozin group than in the placebo group had an improvement in symptom score (58.3% vs 50.9%; odds ratio = 1.15; 95% CI, 1.08-1.23; P < .001). Renal composite outcome did not differ between the 2 treatment groups. Potential adverse effects included volume depletion, renal adverse event, and major hypoglycemia, which occurred at the same rate in the treatment and placebo groups. There was no difference in outcomes or adverse effects between patients with and without diabetes.¹

WHAT'S NEW

Evidence supports dapagliflozin use in a new patient population

The DAPA-HF study compared dapagliflozin to placebo in HF patients both with and without diabetes and demonstrated decreased HF exacerbations and CV deaths, improved ­patient-reported HF symptoms, and lower all-cause mortality in the treatment group. This study supports use of dapagliflozin in a new patient population—those with HF—rather than solely in patients with diabetes, as the drug was originally marketed.

CAVEATS

Specific study population may limit generalizability

The DAPA-HF study included mostly male, White, European patients followed for an average of 18.2 months as part of initial Phase III studies funded by AstraZeneca (the pharmaceutical company that developed dapagliflozin). Given the potential conflict due to funding, all statistical results were verified by an independent academic group, and analyses were completed with an intention-to-treat model. The outlined benefits described here were only studied in a population of patients with reduced EF (≤ 40%), so the impact remains unclear for patients with preserved EF. Safety and benefits beyond 24 months were not studied in this RCT; therefore long-term data are still unknown.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Adding an SGLT2 inhibitor may be cost prohibitive for some patients

An SGLT2 inhibitor costs, on average, $500 to $600 for a 30-day supply, which may be prohibitive for some patients.¹¹ Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications, particularly glucose-lowering therapies, and the optimal prioritization of medications is not yet known.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Some adults who have an intellectual or other developmental disability (IDD) require extensive subspecialty care; many, however, depend primarily on their family physician for the bulk of their health care. With that reliance in mind, this article provides (1) an overview of important services that family physicians can provide for their adult patients with IDD and (2) pragmatic clinical suggestions for tailoring that care. Note: We highlight only some high-impact areas of clinical focus; refer to the 2018 Canadian consensus guidelines for a comprehensive approach to optimizing primary care for this population.¹

CASE

Laura S, a 24-year-old woman with Down syndrome, is visiting your clinic with her mother to establish care. Ms. S has several medical comorbidities, including type 2 diabetes, hyperlipidemia, repaired congenital heart disease, schizoaffective disorder, and hypothyroidism. She is under the care of multiple specialists, including a cardiologist and an endocrinologist. Her medications include the atypical antipsychotic risperidone, which was prescribed for her through the services of a community mental health center.

Ms. S is due for multiple preventive health screenings. She indicates that she feels nervous today talking about these screenings with a new physician.

First step in care: Proficiency in the lexicon of IDD

Three core concepts of IDD are impairment, disability, and handicap. According to the World Health Organization²:

• impairment “is any loss or abnormality of psychological, physiological, or anatomical structure or function.”
• disability “is any restriction or lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a human being.”
• handicap therefore “represents socialization of an impairment or disability, and as such it reflects the consequences for the individual—cultural, social, economic, and environmental—that stem from the presence of impairment and disability.”

Essential transition: Pediatric to adult health care

Health care transition (HCT) is the planned process of transferring care from a pediatric to an adult-based health care setting,³ comprising 3 phases:

• preparation
• transfer from pediatric to adult care
• integration into adult-based care.

Two critical components of a smooth HCT include initiating the transition early in adolescence and providing transition-support resources, which are often lacking, even in large, integrated health systems.⁴ Got Transition, created by the National Alliance to Advance Adolescent Health, outlines core elements of an organized HCT process (www.gottransition.org) specific to young adults with IDD, including young adults with autism spectrum disorder.^5,6 

Even young people who are served by a family physician and who intend to remain in that family practice as they age into adulthood require HCT services that include⁶:

• assessment of readiness to transition to adult care
• update of the medical history
• assessment and promotion of self-care skills
• consent discussions and optimized participation in decision-making
• transition of specialty care from pediatric to adult specialists.

Continue to: For an ideal HCT...

For an ideal health care transition, full engagement of the patient, the medical home, and the patient’s family (including the primary caregiver or guardian) is critical.

For an ideal HCT, full engagement of the patient, the medical home (physicians, nursing staff, and care coordinators), and the patient’s family (including the primary caregiver or guardian) is critical. In addition to preventive care visits and management of chronic disease, additional domains that require explicit attention in transitioning young people with IDD include health insurance, transportation, employment, and postsecondary education.

Young people who have special health care needs and receive high-quality HCT demonstrate improvements in adherence to care, disease-specific measures, quality of life, self-care skills, satisfaction with care, and health care utilization.⁷TABLE 1³ lists resources identified by Berens and colleagues that are helpful in facilitating the transition.

Teach and practice disability etiquette

Societal prejudice harms people with IDD—leading to self-deprecation, alienation from the larger community, and isolation from others with IDD.⁸ To promote acceptance and inclusivity in residential communities, the workplace, recreational venues, and clinical settings, disability etiquette should be utilized—a set of guidelines on how to interact with patients with IDD. These include speaking to the patient directly, using clear language in an adult voice, and avoiding stereotypes about people with disabilities.⁹ The entire health care team, including all front-facing staff (receptionists and care and financial coordinators) and clinical staff (physicians, nurses, medical assistants), need to be educated in, and practice, disability etiquette.

Preparing for in-person visits. Pre-­visit preparation, ideally by means of dialogue between health care staff and the patient or caregiver (or both), typically by telephone and in advance of the scheduled visit, is often critical for a successful first face-to-face encounter. (See “Pre-visit telephone questionnaire and script for a new adult patient with IDD,” page 287, which we developed for use in our office practice.) Outcomes of the pre-visit preparation should include identifying:

• words or actions that can trigger anxiety or panic
• de-escalation techniques, such as specific calming words and actions
• strategies for optimal communication, physical access, and physical examination.

Initial appointments should focus on building trust and rapport with the health care team and desensitizing the patient to the clinical environment.¹⁰ Examination techniques used with pediatric patients can be applied to this population: for example, demonstrating an examination maneuver first on the parent or caregiver; beginning the examination with the least invasive or anxiety-­provoking components; and stating what you plan to do next—before you do it.

Continue to: Systematic health checks provide great value

 

 

Systematic health checks provide great value

A health check is a systematic and comprehensive health assessment that is provided annually to adults with IDD, and includes:

• specific review of signs and symptoms of health conditions that often co-­occur in adults with IDD (TABLE 2Calibri¹¹)
• screening for changes in adaptive functioning and secondary disability
• lifestyle counseling
• medication review and counseling
• immunization update
• discussion of caregiver concerns.

Successful implementation of preventive health screening tests for a patient with IDD often requires ingenuity and creativity to allay fears and anxieties.

Regarding the last point: Many caregivers are the aging parents of the adult patient with IDD—people who have their own emerging health and support needs. You should initiate conversations about advanced planning for the needs of patients, which often involves engaging siblings and other family members to assume a greater role in caregiving.¹²

Benefits of the health check. A systematic review of 38 studies, comprising more than 5000 patients with IDD, found that health checks increased the detection of serious conditions, improved screening for sensory impairments, and increased the immunization rate.¹³ Although many patients with IDD generally understand the need for a periodic health examination, you can enhance their experience by better explaining the rationale for the health check; scheduling sufficient time for the appointment, based on the individual clinical situation; and discussing the value of laboratory testing and referrals to specialists.¹⁴

Tailoring preventive care

Many of the preventive services recommendations typically utilized by family physicians, such as guidelines from the US Preventive Services Task Force, have been developed for the general population at average risk of conditions of interest.¹⁵ Adults with IDD, depending on the cause of their developmental disability and their behavioral risk profile, might be at significantly higher (or lower) risk of cancer, heart disease, or other conditions than the general population. To address these differences, preventive care guidelines tailored to patients with certain developmental disabilities have been created, including guidelines specific to adults with Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, and 22q11.2 deletion (DiGeorge) syndrome.¹⁶

Clarifying the molecular genetic etiology of many developmental disabilities has led to more precise understandings about physical and behavioral health issues associated with specific developmental disabilities. For that reason, patients without a known cause for their IDD might benefit from referral to a geneticist—even in early or middle adulthood. Variables generally associated with a higher likelihood of an abnormal genetic test result include¹⁷:

• a family history of developmental disability
• a congenital malformation or dysmorphic features
• a dual diagnosis of developmental disability and co-occurring mental illness
• hypotonia
• severe or profound IDD.

Continue to: Successful implementation of preventive health screening tests...

Successful implementation of preventive health screening tests often requires ingenuity and the collective creativity of the patient, family members, staff, and family physician to allay fears and anxieties. Examples: Women who have been advised to undergo screening mammography might feel less anxious by undergoing tandem screening with their sister or mother, and colorectal cancer screening might be more easily accomplished using a fecal DNA test rather than by colonoscopy. Procedural desensitization strategies and preventive care instructional materials targeting people with IDD are posted on YouTube (for example, the “DD CARES Best Practices” series [see www.youtube.com/watch?v=EPJy4zvg4io]) and other websites.

Management of chronic disease

Evidence of health disparities in patients with IDD includes suboptimal management of chronic diseases, such as diabetes¹⁸ and hypertension,¹⁹ despite contact with a primary care physician. Nonadherence to a medication regimen might be more common in patients who live with their family or in a residential setting where there is a lower degree of supervision—that is, compared to a residence that maintains 24-hour staffing with daily nursing care and supervision. For a patient who is not so closely supervised, reviewing the medication refill history with the pharmacy, or using the so-called brown-bag technique of counting pill bottles brought to appointments, can ensure medication adherence.

CASE

As you interview Ms. S, you note that she is shy, avoids eye contact, and appears generally anxious. You calm her by noticing and complimenting her jewelry and fingernail polish. Ms. S smiles and talks about her favorite polish colors.

Evaluation of suspected mental and behavioral health issues begins with assessment for medical conditions that might be causing pain and distress or stereotypies.

Her mother reports that, when Ms. S is stressed, she talks to herself alone in her bedroom. However, you do not observe evidence of schizoaffective disorder, and begin to wonder whether she needs to be taking risperidone.

Essentials of mental health care

It is estimated that one-third of adults with IDD have significant mental and behavioral health care needs.²⁰ Patients with IDD suffer the same psychiatric disorders as the general population; some also engage in problematic behaviors, such as self-injurious actions, physical or verbal aggression (or both), property destruction, and resistance to caregiving assistance.

Continue to: Mental and behavioral health problems...

Mental and behavioral health problems can have a profound impact on the quality of life of patients with IDD, their peers, and their family and other caregivers. If untreated, these problems can lead to premature institutionalization, loss of employment or desired program participation, fractured social relationships, and caregiver withdrawal and burnout.

Initial evaluation of suspected mental and behavioral health problems begins with careful assessment for medical conditions that might be causing pain and distress, stereotypies, and other problematic behaviors. Common sources of pain and discomfort include dental and other oral disease, dysphagia, gastroesophageal reflux disease, gastritis, constipation, allergic disease, headache, musculoskeletal pathology, lower urinary tract disease, and gynecologic disorders.¹¹ Identification and optimal treatment of medical conditions might not eliminate problematic behaviors but often decrease their frequency and intensity.

Psychoactive medications are prescribed for many patients with IDD. Many have behavioral adverse effects, such as akathisia, aggression, and disinhibition—leading to a prescribing cascade of psychoactive medication polypharmacy and escalating dosages.²¹ Antipsychotic medications are often initiated without a careful diagnosis, explicit outcome targets, or adequate clinical monitoring for effectiveness; in addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.²¹ Even a family physician who is not the prescriber can perform an important advocacy role by critically reviewing psychoactive medications, documenting adverse effects, insisting on a clear therapeutic target, and calling for discontinuation of medications that appear to be ineffective.

Evaluation of mental and behavioral health problems requires a developmental perspective to interpret specific, observable behaviors with a proper clinical lens. For example, many patients with IDD engage in self-talk (soliloquizing) as a means of processing the world around them. This practice might escalate during a time of physical or psychological stress, and the unwary clinician might misinterpret this behavior as psychotic, leading to inappropriate prescribing of antipsychotic medication. Other psychotoform behaviors that, superficially, mimic but are typically not truly psychotic, include talk with or about imaginary friends and repetitive retelling of sometimes elaborate or grandiose tales or assertions. The failure of clinicians to recognize developmentally determined expressions of distress often leads to a misdiagnosis of schizophrenia or other psychotic illness and, consequently, inappropriate psychopharmacotherapy. 

Family physicians, familiar with the use of psychiatric scales for diagnosis and treatment monitoring, should use similar scales that have been developed specifically for patients with IDD (TABLE 3¹¹). In addition, a psychiatric diagnosis manual, the Diagnostic Manual—Intellectual Disability 2, specific to people with IDD (and analogous to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) provides modification of diagnostic criteria to account for patients who have difficulty articulating their internal emotional state and inner thoughts.²²

Continue to: Problematic behaviors

Problematic behaviors that are not features of a bona fide psychiatric disorder are often best understood through functional behavioral analysis, which examines antecedents and consequences of problematic behaviors and identifies their predictable outcomes, such as gaining attention, avoiding a task, or securing a desired item. Rather than being given a prescription for psychoactive medication, many adult patients with IDD and problematic behaviors might be best served by having you order consultation with a certified behavior analyst. The analyst will conduct an evaluation and, along with family or residential staff and the patient, craft a behavioral support plan to address core drivers of the undesired behavior. Behavioral support plans might be enriched by multidisciplinary input from a speech and language pathologist, habilitation professionals, occupational and physical therapists, a neuropsychologist, and others.²³

Antipsychotic medications are often initiated without a careful diagnosis. In addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.

Resources to help you address the physical, mental, and behavioral health problems of these patients are available online through Vanderbilt Kennedy Center’s “Toolkit for primary care providers” (https://iddtoolkit.vkcsites.org).

CASE

During your examination, you review Ms. S’s vital signs, including body mass index (BMI). You calculate that she is morbidly obese—BMI, 37—in the setting of a known comorbidity, diabetes.

Ms. S tells you that she is interested in having a healthy lifestyle, but feels frustrated because she does not know how to make the necessary changes. You discuss with her how some medications, including risperidone, can promote weight gain, and that it is important for her mental health provider to carefully reassess whether she needs to continue the drug.

Weight management in a patient population that tends to be sedentary

Patients with IDD are more likely to live a sedentary lifestyle. Compared to adults who do not have IDD, adults with IDD—especially women and patients with Down syndrome—are reported to have a higher prevalence of obesity.²⁴

Continue to: As in the general population...

Similarly, undesired weight loss demands careful evaluation and management because such loss can reflect a medically significant condition, such as gastroesophageal reflux, constipation, dysphagia, neglect, and cancer.²⁷

Boosting the amount and effectiveness of physical activity

Young people with IDD participate in physical activity less often than their neurotypical peers; as a result, they tend to be less fit and have a higher prevalence of obesity.²⁸ Based on a meta-analysis, interventions that focus on sport and movement skills training, such as soccer, basketball, and ball-throwing programs, might be more effective than general physical activity programs.²⁸ In addition to year-round sports training and athletic competitions, Special Olympics conducts vital health screenings of athletes and supports community-based initiatives that address bias against patients with IDD, promote inclusion, and foster social relationships (www.specialolympics.org/our-work/inclusive-health?locale=en).

Success in weight management involves multidisciplinary treatment, including nutritional support, physical activity, behavioral changes, and close follow-up.

Emphasize regular activity. In adulthood, fewer than 10% of patients with IDD exercise regularly.²¹ According to the second edition of Physical Activity Guidelines for Americans,²⁹ “all adults, with or without a disability, should get at least 150 minutes of aerobic physical activity a week. Activities can be broken down into smaller amounts, such as about 25 minutes a day every day.”³⁰ Supplementation with muscle-strengthening activities (eg, yoga, weight training, and resistance-band training) provides further health benefit, such as improvement in posture and prevention of future injury.³¹ An ideal exercise program proposed by Tyler and Baker is based on a daily, “3-2-1” schedule (ie, of every hour of activity, 30 minutes should be of aerobic exercise; 20 minutes, of strength building; and 10 minutes, of flexibility).¹¹ By participating in any type of physical activity, there is potential for considerable health benefit in reducing psychosocial stressors, improving mental health, counteracting metabolic syndromes, and, ultimately, reducing morbidity and mortality related to physical inactivity.

CASE

With permission from Ms. S, you send your progress notes by fax to her mental health provider at the community mental health center and request a call to discuss her case—in particular, to examine potential alternatives to risperidone. With Ms. S’s input, you also co-create an exercise prescription that includes a daily 20-minute walking program with her mother.

At the follow-up visit that is scheduled in 3 months, you anticipate adding a resistance component and balance activity to the exercise prescription to enrich Ms. S’s physical activity regimen.

CORRESPONDENCE
Carl V. Tyler Jr., MD, 14601 Detroit Avenue, Lakewood, OH, 44107; [email protected]

Some adults who have an intellectual or other developmental disability (IDD) require extensive subspecialty care; many, however, depend primarily on their family physician for the bulk of their health care. With that reliance in mind, this article provides (1) an overview of important services that family physicians can provide for their adult patients with IDD and (2) pragmatic clinical suggestions for tailoring that care. Note: We highlight only some high-impact areas of clinical focus; refer to the 2018 Canadian consensus guidelines for a comprehensive approach to optimizing primary care for this population.¹

CASE

Laura S, a 24-year-old woman with Down syndrome, is visiting your clinic with her mother to establish care. Ms. S has several medical comorbidities, including type 2 diabetes, hyperlipidemia, repaired congenital heart disease, schizoaffective disorder, and hypothyroidism. She is under the care of multiple specialists, including a cardiologist and an endocrinologist. Her medications include the atypical antipsychotic risperidone, which was prescribed for her through the services of a community mental health center.

Ms. S is due for multiple preventive health screenings. She indicates that she feels nervous today talking about these screenings with a new physician.

First step in care: Proficiency in the lexicon of IDD

Three core concepts of IDD are impairment, disability, and handicap. According to the World Health Organization²:

• impairment “is any loss or abnormality of psychological, physiological, or anatomical structure or function.”
• disability “is any restriction or lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a human being.”
• handicap therefore “represents socialization of an impairment or disability, and as such it reflects the consequences for the individual—cultural, social, economic, and environmental—that stem from the presence of impairment and disability.”

Essential transition: Pediatric to adult health care

Health care transition (HCT) is the planned process of transferring care from a pediatric to an adult-based health care setting,³ comprising 3 phases:

• preparation
• transfer from pediatric to adult care
• integration into adult-based care.

Two critical components of a smooth HCT include initiating the transition early in adolescence and providing transition-support resources, which are often lacking, even in large, integrated health systems.⁴ Got Transition, created by the National Alliance to Advance Adolescent Health, outlines core elements of an organized HCT process (www.gottransition.org) specific to young adults with IDD, including young adults with autism spectrum disorder.^5,6 

Even young people who are served by a family physician and who intend to remain in that family practice as they age into adulthood require HCT services that include⁶:

• assessment of readiness to transition to adult care
• update of the medical history
• assessment and promotion of self-care skills
• consent discussions and optimized participation in decision-making
• transition of specialty care from pediatric to adult specialists.

Continue to: For an ideal HCT...

For an ideal health care transition, full engagement of the patient, the medical home, and the patient’s family (including the primary caregiver or guardian) is critical.

For an ideal HCT, full engagement of the patient, the medical home (physicians, nursing staff, and care coordinators), and the patient’s family (including the primary caregiver or guardian) is critical. In addition to preventive care visits and management of chronic disease, additional domains that require explicit attention in transitioning young people with IDD include health insurance, transportation, employment, and postsecondary education.

Young people who have special health care needs and receive high-quality HCT demonstrate improvements in adherence to care, disease-specific measures, quality of life, self-care skills, satisfaction with care, and health care utilization.⁷TABLE 1³ lists resources identified by Berens and colleagues that are helpful in facilitating the transition.

Teach and practice disability etiquette

Societal prejudice harms people with IDD—leading to self-deprecation, alienation from the larger community, and isolation from others with IDD.⁸ To promote acceptance and inclusivity in residential communities, the workplace, recreational venues, and clinical settings, disability etiquette should be utilized—a set of guidelines on how to interact with patients with IDD. These include speaking to the patient directly, using clear language in an adult voice, and avoiding stereotypes about people with disabilities.⁹ The entire health care team, including all front-facing staff (receptionists and care and financial coordinators) and clinical staff (physicians, nurses, medical assistants), need to be educated in, and practice, disability etiquette.

Preparing for in-person visits. Pre-­visit preparation, ideally by means of dialogue between health care staff and the patient or caregiver (or both), typically by telephone and in advance of the scheduled visit, is often critical for a successful first face-to-face encounter. (See “Pre-visit telephone questionnaire and script for a new adult patient with IDD,” page 287, which we developed for use in our office practice.) Outcomes of the pre-visit preparation should include identifying:

• words or actions that can trigger anxiety or panic
• de-escalation techniques, such as specific calming words and actions
• strategies for optimal communication, physical access, and physical examination.

Initial appointments should focus on building trust and rapport with the health care team and desensitizing the patient to the clinical environment.¹⁰ Examination techniques used with pediatric patients can be applied to this population: for example, demonstrating an examination maneuver first on the parent or caregiver; beginning the examination with the least invasive or anxiety-­provoking components; and stating what you plan to do next—before you do it.

Continue to: Systematic health checks provide great value

 

 

Systematic health checks provide great value

A health check is a systematic and comprehensive health assessment that is provided annually to adults with IDD, and includes:

• specific review of signs and symptoms of health conditions that often co-­occur in adults with IDD (TABLE 2Calibri¹¹)
• screening for changes in adaptive functioning and secondary disability
• lifestyle counseling
• medication review and counseling
• immunization update
• discussion of caregiver concerns.

Successful implementation of preventive health screening tests for a patient with IDD often requires ingenuity and creativity to allay fears and anxieties.

Regarding the last point: Many caregivers are the aging parents of the adult patient with IDD—people who have their own emerging health and support needs. You should initiate conversations about advanced planning for the needs of patients, which often involves engaging siblings and other family members to assume a greater role in caregiving.¹²

Benefits of the health check. A systematic review of 38 studies, comprising more than 5000 patients with IDD, found that health checks increased the detection of serious conditions, improved screening for sensory impairments, and increased the immunization rate.¹³ Although many patients with IDD generally understand the need for a periodic health examination, you can enhance their experience by better explaining the rationale for the health check; scheduling sufficient time for the appointment, based on the individual clinical situation; and discussing the value of laboratory testing and referrals to specialists.¹⁴

Tailoring preventive care

Many of the preventive services recommendations typically utilized by family physicians, such as guidelines from the US Preventive Services Task Force, have been developed for the general population at average risk of conditions of interest.¹⁵ Adults with IDD, depending on the cause of their developmental disability and their behavioral risk profile, might be at significantly higher (or lower) risk of cancer, heart disease, or other conditions than the general population. To address these differences, preventive care guidelines tailored to patients with certain developmental disabilities have been created, including guidelines specific to adults with Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, and 22q11.2 deletion (DiGeorge) syndrome.¹⁶

Clarifying the molecular genetic etiology of many developmental disabilities has led to more precise understandings about physical and behavioral health issues associated with specific developmental disabilities. For that reason, patients without a known cause for their IDD might benefit from referral to a geneticist—even in early or middle adulthood. Variables generally associated with a higher likelihood of an abnormal genetic test result include¹⁷:

• a family history of developmental disability
• a congenital malformation or dysmorphic features
• a dual diagnosis of developmental disability and co-occurring mental illness
• hypotonia
• severe or profound IDD.

Continue to: Successful implementation of preventive health screening tests...

Successful implementation of preventive health screening tests often requires ingenuity and the collective creativity of the patient, family members, staff, and family physician to allay fears and anxieties. Examples: Women who have been advised to undergo screening mammography might feel less anxious by undergoing tandem screening with their sister or mother, and colorectal cancer screening might be more easily accomplished using a fecal DNA test rather than by colonoscopy. Procedural desensitization strategies and preventive care instructional materials targeting people with IDD are posted on YouTube (for example, the “DD CARES Best Practices” series [see www.youtube.com/watch?v=EPJy4zvg4io]) and other websites.

Management of chronic disease

Evidence of health disparities in patients with IDD includes suboptimal management of chronic diseases, such as diabetes¹⁸ and hypertension,¹⁹ despite contact with a primary care physician. Nonadherence to a medication regimen might be more common in patients who live with their family or in a residential setting where there is a lower degree of supervision—that is, compared to a residence that maintains 24-hour staffing with daily nursing care and supervision. For a patient who is not so closely supervised, reviewing the medication refill history with the pharmacy, or using the so-called brown-bag technique of counting pill bottles brought to appointments, can ensure medication adherence.

CASE

As you interview Ms. S, you note that she is shy, avoids eye contact, and appears generally anxious. You calm her by noticing and complimenting her jewelry and fingernail polish. Ms. S smiles and talks about her favorite polish colors.

Evaluation of suspected mental and behavioral health issues begins with assessment for medical conditions that might be causing pain and distress or stereotypies.

Her mother reports that, when Ms. S is stressed, she talks to herself alone in her bedroom. However, you do not observe evidence of schizoaffective disorder, and begin to wonder whether she needs to be taking risperidone.

Essentials of mental health care

It is estimated that one-third of adults with IDD have significant mental and behavioral health care needs.²⁰ Patients with IDD suffer the same psychiatric disorders as the general population; some also engage in problematic behaviors, such as self-injurious actions, physical or verbal aggression (or both), property destruction, and resistance to caregiving assistance.

Continue to: Mental and behavioral health problems...

Mental and behavioral health problems can have a profound impact on the quality of life of patients with IDD, their peers, and their family and other caregivers. If untreated, these problems can lead to premature institutionalization, loss of employment or desired program participation, fractured social relationships, and caregiver withdrawal and burnout.

Initial evaluation of suspected mental and behavioral health problems begins with careful assessment for medical conditions that might be causing pain and distress, stereotypies, and other problematic behaviors. Common sources of pain and discomfort include dental and other oral disease, dysphagia, gastroesophageal reflux disease, gastritis, constipation, allergic disease, headache, musculoskeletal pathology, lower urinary tract disease, and gynecologic disorders.¹¹ Identification and optimal treatment of medical conditions might not eliminate problematic behaviors but often decrease their frequency and intensity.

Psychoactive medications are prescribed for many patients with IDD. Many have behavioral adverse effects, such as akathisia, aggression, and disinhibition—leading to a prescribing cascade of psychoactive medication polypharmacy and escalating dosages.²¹ Antipsychotic medications are often initiated without a careful diagnosis, explicit outcome targets, or adequate clinical monitoring for effectiveness; in addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.²¹ Even a family physician who is not the prescriber can perform an important advocacy role by critically reviewing psychoactive medications, documenting adverse effects, insisting on a clear therapeutic target, and calling for discontinuation of medications that appear to be ineffective.

Evaluation of mental and behavioral health problems requires a developmental perspective to interpret specific, observable behaviors with a proper clinical lens. For example, many patients with IDD engage in self-talk (soliloquizing) as a means of processing the world around them. This practice might escalate during a time of physical or psychological stress, and the unwary clinician might misinterpret this behavior as psychotic, leading to inappropriate prescribing of antipsychotic medication. Other psychotoform behaviors that, superficially, mimic but are typically not truly psychotic, include talk with or about imaginary friends and repetitive retelling of sometimes elaborate or grandiose tales or assertions. The failure of clinicians to recognize developmentally determined expressions of distress often leads to a misdiagnosis of schizophrenia or other psychotic illness and, consequently, inappropriate psychopharmacotherapy. 

Family physicians, familiar with the use of psychiatric scales for diagnosis and treatment monitoring, should use similar scales that have been developed specifically for patients with IDD (TABLE 3¹¹). In addition, a psychiatric diagnosis manual, the Diagnostic Manual—Intellectual Disability 2, specific to people with IDD (and analogous to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) provides modification of diagnostic criteria to account for patients who have difficulty articulating their internal emotional state and inner thoughts.²²

Continue to: Problematic behaviors

Problematic behaviors that are not features of a bona fide psychiatric disorder are often best understood through functional behavioral analysis, which examines antecedents and consequences of problematic behaviors and identifies their predictable outcomes, such as gaining attention, avoiding a task, or securing a desired item. Rather than being given a prescription for psychoactive medication, many adult patients with IDD and problematic behaviors might be best served by having you order consultation with a certified behavior analyst. The analyst will conduct an evaluation and, along with family or residential staff and the patient, craft a behavioral support plan to address core drivers of the undesired behavior. Behavioral support plans might be enriched by multidisciplinary input from a speech and language pathologist, habilitation professionals, occupational and physical therapists, a neuropsychologist, and others.²³

Antipsychotic medications are often initiated without a careful diagnosis. In addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.

Resources to help you address the physical, mental, and behavioral health problems of these patients are available online through Vanderbilt Kennedy Center’s “Toolkit for primary care providers” (https://iddtoolkit.vkcsites.org).

CASE

During your examination, you review Ms. S’s vital signs, including body mass index (BMI). You calculate that she is morbidly obese—BMI, 37—in the setting of a known comorbidity, diabetes.

Ms. S tells you that she is interested in having a healthy lifestyle, but feels frustrated because she does not know how to make the necessary changes. You discuss with her how some medications, including risperidone, can promote weight gain, and that it is important for her mental health provider to carefully reassess whether she needs to continue the drug.

Weight management in a patient population that tends to be sedentary

Patients with IDD are more likely to live a sedentary lifestyle. Compared to adults who do not have IDD, adults with IDD—especially women and patients with Down syndrome—are reported to have a higher prevalence of obesity.²⁴

Continue to: As in the general population...

Similarly, undesired weight loss demands careful evaluation and management because such loss can reflect a medically significant condition, such as gastroesophageal reflux, constipation, dysphagia, neglect, and cancer.²⁷

Boosting the amount and effectiveness of physical activity

Young people with IDD participate in physical activity less often than their neurotypical peers; as a result, they tend to be less fit and have a higher prevalence of obesity.²⁸ Based on a meta-analysis, interventions that focus on sport and movement skills training, such as soccer, basketball, and ball-throwing programs, might be more effective than general physical activity programs.²⁸ In addition to year-round sports training and athletic competitions, Special Olympics conducts vital health screenings of athletes and supports community-based initiatives that address bias against patients with IDD, promote inclusion, and foster social relationships (www.specialolympics.org/our-work/inclusive-health?locale=en).

Success in weight management involves multidisciplinary treatment, including nutritional support, physical activity, behavioral changes, and close follow-up.

Emphasize regular activity. In adulthood, fewer than 10% of patients with IDD exercise regularly.²¹ According to the second edition of Physical Activity Guidelines for Americans,²⁹ “all adults, with or without a disability, should get at least 150 minutes of aerobic physical activity a week. Activities can be broken down into smaller amounts, such as about 25 minutes a day every day.”³⁰ Supplementation with muscle-strengthening activities (eg, yoga, weight training, and resistance-band training) provides further health benefit, such as improvement in posture and prevention of future injury.³¹ An ideal exercise program proposed by Tyler and Baker is based on a daily, “3-2-1” schedule (ie, of every hour of activity, 30 minutes should be of aerobic exercise; 20 minutes, of strength building; and 10 minutes, of flexibility).¹¹ By participating in any type of physical activity, there is potential for considerable health benefit in reducing psychosocial stressors, improving mental health, counteracting metabolic syndromes, and, ultimately, reducing morbidity and mortality related to physical inactivity.

CASE

With permission from Ms. S, you send your progress notes by fax to her mental health provider at the community mental health center and request a call to discuss her case—in particular, to examine potential alternatives to risperidone. With Ms. S’s input, you also co-create an exercise prescription that includes a daily 20-minute walking program with her mother.

At the follow-up visit that is scheduled in 3 months, you anticipate adding a resistance component and balance activity to the exercise prescription to enrich Ms. S’s physical activity regimen.

CORRESPONDENCE
Carl V. Tyler Jr., MD, 14601 Detroit Avenue, Lakewood, OH, 44107; [email protected]

Some adults who have an intellectual or other developmental disability (IDD) require extensive subspecialty care; many, however, depend primarily on their family physician for the bulk of their health care. With that reliance in mind, this article provides (1) an overview of important services that family physicians can provide for their adult patients with IDD and (2) pragmatic clinical suggestions for tailoring that care. Note: We highlight only some high-impact areas of clinical focus; refer to the 2018 Canadian consensus guidelines for a comprehensive approach to optimizing primary care for this population.¹

CASE

Laura S, a 24-year-old woman with Down syndrome, is visiting your clinic with her mother to establish care. Ms. S has several medical comorbidities, including type 2 diabetes, hyperlipidemia, repaired congenital heart disease, schizoaffective disorder, and hypothyroidism. She is under the care of multiple specialists, including a cardiologist and an endocrinologist. Her medications include the atypical antipsychotic risperidone, which was prescribed for her through the services of a community mental health center.

Ms. S is due for multiple preventive health screenings. She indicates that she feels nervous today talking about these screenings with a new physician.

First step in care: Proficiency in the lexicon of IDD

Three core concepts of IDD are impairment, disability, and handicap. According to the World Health Organization²:

• impairment “is any loss or abnormality of psychological, physiological, or anatomical structure or function.”
• disability “is any restriction or lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a human being.”
• handicap therefore “represents socialization of an impairment or disability, and as such it reflects the consequences for the individual—cultural, social, economic, and environmental—that stem from the presence of impairment and disability.”

Essential transition: Pediatric to adult health care

Health care transition (HCT) is the planned process of transferring care from a pediatric to an adult-based health care setting,³ comprising 3 phases:

• preparation
• transfer from pediatric to adult care
• integration into adult-based care.

Two critical components of a smooth HCT include initiating the transition early in adolescence and providing transition-support resources, which are often lacking, even in large, integrated health systems.⁴ Got Transition, created by the National Alliance to Advance Adolescent Health, outlines core elements of an organized HCT process (www.gottransition.org) specific to young adults with IDD, including young adults with autism spectrum disorder.^5,6 

Even young people who are served by a family physician and who intend to remain in that family practice as they age into adulthood require HCT services that include⁶:

• assessment of readiness to transition to adult care
• update of the medical history
• assessment and promotion of self-care skills
• consent discussions and optimized participation in decision-making
• transition of specialty care from pediatric to adult specialists.

Continue to: For an ideal HCT...

For an ideal health care transition, full engagement of the patient, the medical home, and the patient’s family (including the primary caregiver or guardian) is critical.

For an ideal HCT, full engagement of the patient, the medical home (physicians, nursing staff, and care coordinators), and the patient’s family (including the primary caregiver or guardian) is critical. In addition to preventive care visits and management of chronic disease, additional domains that require explicit attention in transitioning young people with IDD include health insurance, transportation, employment, and postsecondary education.

Young people who have special health care needs and receive high-quality HCT demonstrate improvements in adherence to care, disease-specific measures, quality of life, self-care skills, satisfaction with care, and health care utilization.⁷TABLE 1³ lists resources identified by Berens and colleagues that are helpful in facilitating the transition.

Teach and practice disability etiquette

Societal prejudice harms people with IDD—leading to self-deprecation, alienation from the larger community, and isolation from others with IDD.⁸ To promote acceptance and inclusivity in residential communities, the workplace, recreational venues, and clinical settings, disability etiquette should be utilized—a set of guidelines on how to interact with patients with IDD. These include speaking to the patient directly, using clear language in an adult voice, and avoiding stereotypes about people with disabilities.⁹ The entire health care team, including all front-facing staff (receptionists and care and financial coordinators) and clinical staff (physicians, nurses, medical assistants), need to be educated in, and practice, disability etiquette.

Preparing for in-person visits. Pre-­visit preparation, ideally by means of dialogue between health care staff and the patient or caregiver (or both), typically by telephone and in advance of the scheduled visit, is often critical for a successful first face-to-face encounter. (See “Pre-visit telephone questionnaire and script for a new adult patient with IDD,” page 287, which we developed for use in our office practice.) Outcomes of the pre-visit preparation should include identifying:

• words or actions that can trigger anxiety or panic
• de-escalation techniques, such as specific calming words and actions
• strategies for optimal communication, physical access, and physical examination.

Initial appointments should focus on building trust and rapport with the health care team and desensitizing the patient to the clinical environment.¹⁰ Examination techniques used with pediatric patients can be applied to this population: for example, demonstrating an examination maneuver first on the parent or caregiver; beginning the examination with the least invasive or anxiety-­provoking components; and stating what you plan to do next—before you do it.

Continue to: Systematic health checks provide great value

 

 

Systematic health checks provide great value

A health check is a systematic and comprehensive health assessment that is provided annually to adults with IDD, and includes:

• specific review of signs and symptoms of health conditions that often co-­occur in adults with IDD (TABLE 2Calibri¹¹)
• screening for changes in adaptive functioning and secondary disability
• lifestyle counseling
• medication review and counseling
• immunization update
• discussion of caregiver concerns.

Successful implementation of preventive health screening tests for a patient with IDD often requires ingenuity and creativity to allay fears and anxieties.

Regarding the last point: Many caregivers are the aging parents of the adult patient with IDD—people who have their own emerging health and support needs. You should initiate conversations about advanced planning for the needs of patients, which often involves engaging siblings and other family members to assume a greater role in caregiving.¹²

Benefits of the health check. A systematic review of 38 studies, comprising more than 5000 patients with IDD, found that health checks increased the detection of serious conditions, improved screening for sensory impairments, and increased the immunization rate.¹³ Although many patients with IDD generally understand the need for a periodic health examination, you can enhance their experience by better explaining the rationale for the health check; scheduling sufficient time for the appointment, based on the individual clinical situation; and discussing the value of laboratory testing and referrals to specialists.¹⁴

Tailoring preventive care

Many of the preventive services recommendations typically utilized by family physicians, such as guidelines from the US Preventive Services Task Force, have been developed for the general population at average risk of conditions of interest.¹⁵ Adults with IDD, depending on the cause of their developmental disability and their behavioral risk profile, might be at significantly higher (or lower) risk of cancer, heart disease, or other conditions than the general population. To address these differences, preventive care guidelines tailored to patients with certain developmental disabilities have been created, including guidelines specific to adults with Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, and 22q11.2 deletion (DiGeorge) syndrome.¹⁶

Clarifying the molecular genetic etiology of many developmental disabilities has led to more precise understandings about physical and behavioral health issues associated with specific developmental disabilities. For that reason, patients without a known cause for their IDD might benefit from referral to a geneticist—even in early or middle adulthood. Variables generally associated with a higher likelihood of an abnormal genetic test result include¹⁷:

• a family history of developmental disability
• a congenital malformation or dysmorphic features
• a dual diagnosis of developmental disability and co-occurring mental illness
• hypotonia
• severe or profound IDD.

Continue to: Successful implementation of preventive health screening tests...

Successful implementation of preventive health screening tests often requires ingenuity and the collective creativity of the patient, family members, staff, and family physician to allay fears and anxieties. Examples: Women who have been advised to undergo screening mammography might feel less anxious by undergoing tandem screening with their sister or mother, and colorectal cancer screening might be more easily accomplished using a fecal DNA test rather than by colonoscopy. Procedural desensitization strategies and preventive care instructional materials targeting people with IDD are posted on YouTube (for example, the “DD CARES Best Practices” series [see www.youtube.com/watch?v=EPJy4zvg4io]) and other websites.

Management of chronic disease

Evidence of health disparities in patients with IDD includes suboptimal management of chronic diseases, such as diabetes¹⁸ and hypertension,¹⁹ despite contact with a primary care physician. Nonadherence to a medication regimen might be more common in patients who live with their family or in a residential setting where there is a lower degree of supervision—that is, compared to a residence that maintains 24-hour staffing with daily nursing care and supervision. For a patient who is not so closely supervised, reviewing the medication refill history with the pharmacy, or using the so-called brown-bag technique of counting pill bottles brought to appointments, can ensure medication adherence.

CASE

As you interview Ms. S, you note that she is shy, avoids eye contact, and appears generally anxious. You calm her by noticing and complimenting her jewelry and fingernail polish. Ms. S smiles and talks about her favorite polish colors.

Evaluation of suspected mental and behavioral health issues begins with assessment for medical conditions that might be causing pain and distress or stereotypies.

Her mother reports that, when Ms. S is stressed, she talks to herself alone in her bedroom. However, you do not observe evidence of schizoaffective disorder, and begin to wonder whether she needs to be taking risperidone.

Essentials of mental health care

It is estimated that one-third of adults with IDD have significant mental and behavioral health care needs.²⁰ Patients with IDD suffer the same psychiatric disorders as the general population; some also engage in problematic behaviors, such as self-injurious actions, physical or verbal aggression (or both), property destruction, and resistance to caregiving assistance.

Continue to: Mental and behavioral health problems...

Mental and behavioral health problems can have a profound impact on the quality of life of patients with IDD, their peers, and their family and other caregivers. If untreated, these problems can lead to premature institutionalization, loss of employment or desired program participation, fractured social relationships, and caregiver withdrawal and burnout.

Initial evaluation of suspected mental and behavioral health problems begins with careful assessment for medical conditions that might be causing pain and distress, stereotypies, and other problematic behaviors. Common sources of pain and discomfort include dental and other oral disease, dysphagia, gastroesophageal reflux disease, gastritis, constipation, allergic disease, headache, musculoskeletal pathology, lower urinary tract disease, and gynecologic disorders.¹¹ Identification and optimal treatment of medical conditions might not eliminate problematic behaviors but often decrease their frequency and intensity.

Psychoactive medications are prescribed for many patients with IDD. Many have behavioral adverse effects, such as akathisia, aggression, and disinhibition—leading to a prescribing cascade of psychoactive medication polypharmacy and escalating dosages.²¹ Antipsychotic medications are often initiated without a careful diagnosis, explicit outcome targets, or adequate clinical monitoring for effectiveness; in addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.²¹ Even a family physician who is not the prescriber can perform an important advocacy role by critically reviewing psychoactive medications, documenting adverse effects, insisting on a clear therapeutic target, and calling for discontinuation of medications that appear to be ineffective.

Evaluation of mental and behavioral health problems requires a developmental perspective to interpret specific, observable behaviors with a proper clinical lens. For example, many patients with IDD engage in self-talk (soliloquizing) as a means of processing the world around them. This practice might escalate during a time of physical or psychological stress, and the unwary clinician might misinterpret this behavior as psychotic, leading to inappropriate prescribing of antipsychotic medication. Other psychotoform behaviors that, superficially, mimic but are typically not truly psychotic, include talk with or about imaginary friends and repetitive retelling of sometimes elaborate or grandiose tales or assertions. The failure of clinicians to recognize developmentally determined expressions of distress often leads to a misdiagnosis of schizophrenia or other psychotic illness and, consequently, inappropriate psychopharmacotherapy. 

Family physicians, familiar with the use of psychiatric scales for diagnosis and treatment monitoring, should use similar scales that have been developed specifically for patients with IDD (TABLE 3¹¹). In addition, a psychiatric diagnosis manual, the Diagnostic Manual—Intellectual Disability 2, specific to people with IDD (and analogous to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) provides modification of diagnostic criteria to account for patients who have difficulty articulating their internal emotional state and inner thoughts.²²

Continue to: Problematic behaviors

Problematic behaviors that are not features of a bona fide psychiatric disorder are often best understood through functional behavioral analysis, which examines antecedents and consequences of problematic behaviors and identifies their predictable outcomes, such as gaining attention, avoiding a task, or securing a desired item. Rather than being given a prescription for psychoactive medication, many adult patients with IDD and problematic behaviors might be best served by having you order consultation with a certified behavior analyst. The analyst will conduct an evaluation and, along with family or residential staff and the patient, craft a behavioral support plan to address core drivers of the undesired behavior. Behavioral support plans might be enriched by multidisciplinary input from a speech and language pathologist, habilitation professionals, occupational and physical therapists, a neuropsychologist, and others.²³

Antipsychotic medications are often initiated without a careful diagnosis. In addition, they often lead to insulin resistance, metabolic syndrome, and massive weight gain.

Resources to help you address the physical, mental, and behavioral health problems of these patients are available online through Vanderbilt Kennedy Center’s “Toolkit for primary care providers” (https://iddtoolkit.vkcsites.org).

CASE

During your examination, you review Ms. S’s vital signs, including body mass index (BMI). You calculate that she is morbidly obese—BMI, 37—in the setting of a known comorbidity, diabetes.

Ms. S tells you that she is interested in having a healthy lifestyle, but feels frustrated because she does not know how to make the necessary changes. You discuss with her how some medications, including risperidone, can promote weight gain, and that it is important for her mental health provider to carefully reassess whether she needs to continue the drug.

Weight management in a patient population that tends to be sedentary

Patients with IDD are more likely to live a sedentary lifestyle. Compared to adults who do not have IDD, adults with IDD—especially women and patients with Down syndrome—are reported to have a higher prevalence of obesity.²⁴

Continue to: As in the general population...

Similarly, undesired weight loss demands careful evaluation and management because such loss can reflect a medically significant condition, such as gastroesophageal reflux, constipation, dysphagia, neglect, and cancer.²⁷

Boosting the amount and effectiveness of physical activity

Young people with IDD participate in physical activity less often than their neurotypical peers; as a result, they tend to be less fit and have a higher prevalence of obesity.²⁸ Based on a meta-analysis, interventions that focus on sport and movement skills training, such as soccer, basketball, and ball-throwing programs, might be more effective than general physical activity programs.²⁸ In addition to year-round sports training and athletic competitions, Special Olympics conducts vital health screenings of athletes and supports community-based initiatives that address bias against patients with IDD, promote inclusion, and foster social relationships (www.specialolympics.org/our-work/inclusive-health?locale=en).

Success in weight management involves multidisciplinary treatment, including nutritional support, physical activity, behavioral changes, and close follow-up.

Emphasize regular activity. In adulthood, fewer than 10% of patients with IDD exercise regularly.²¹ According to the second edition of Physical Activity Guidelines for Americans,²⁹ “all adults, with or without a disability, should get at least 150 minutes of aerobic physical activity a week. Activities can be broken down into smaller amounts, such as about 25 minutes a day every day.”³⁰ Supplementation with muscle-strengthening activities (eg, yoga, weight training, and resistance-band training) provides further health benefit, such as improvement in posture and prevention of future injury.³¹ An ideal exercise program proposed by Tyler and Baker is based on a daily, “3-2-1” schedule (ie, of every hour of activity, 30 minutes should be of aerobic exercise; 20 minutes, of strength building; and 10 minutes, of flexibility).¹¹ By participating in any type of physical activity, there is potential for considerable health benefit in reducing psychosocial stressors, improving mental health, counteracting metabolic syndromes, and, ultimately, reducing morbidity and mortality related to physical inactivity.

CASE

With permission from Ms. S, you send your progress notes by fax to her mental health provider at the community mental health center and request a call to discuss her case—in particular, to examine potential alternatives to risperidone. With Ms. S’s input, you also co-create an exercise prescription that includes a daily 20-minute walking program with her mother.

At the follow-up visit that is scheduled in 3 months, you anticipate adding a resistance component and balance activity to the exercise prescription to enrich Ms. S’s physical activity regimen.

CORRESPONDENCE
Carl V. Tyler Jr., MD, 14601 Detroit Avenue, Lakewood, OH, 44107; [email protected]

Bicycle riding may help people with diabetes live longer, new research suggests.

NicolasMcComber/E+/Getty Images

Among more than 7,000 adults with diabetes in 10 Western European countries followed for about 15 years, those who cycled regularly were significantly less likely to die of any cause or of cardiovascular causes, even after accounting for differences in factors such as sex, age, educational level, diet, comorbidities, and other physical activities.

“The association between cycling and all-cause and CVD [cardiovascular disease] mortality in this study of person[s] with diabetes was of the same magnitude and direction as observed in the healthy population,” wrote Mathias Ried-Larsen, PhD, of the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and colleagues. The findings were published online July 19, 2021, in JAMA Internal Medicine.

In an accompanying Editor’s Note, JAMA Internal Medicine editor Rita F. Redberg, MD, and two deputy editors said that the new data add to previous studies showing benefits of cycling, compared with other physical activities. “The analysis from Ried-Larsen and colleagues strengthens the epidemiologic data on cycling and strongly suggests that it may contribute directly to longer and healthier lives,” they wrote.

Dr. Redberg, of the University of California, San Francisco, told this news organization: “I think the number of cyclists grew greatly during pandemic, when there was little auto traffic, and people did not want to take public transportation. Cities that add bike lanes, especially protected bike lanes, see an increase in cyclists. I think Americans can cycle more, would enjoy cycling more, and would live longer [by] cycling, to work and for pleasure.”

Dr. Redberg disclosed that she is “an avid cyclist and am currently on a bike ride in Glacier National Park. ... This group [Climate Ride] raises money for more bike lanes, promotes climate change awareness, has paid for solar panels at Glacier, and more.”

However, Dr. Redberg and colleagues also “recognize that cycling requires fitness, a good sense of balance, and the means to purchase a bicycle. We also understand that regular cycling requires living in an area where it is reasonably safe, and we celebrate the installation of more bike lanes, particularly protected lanes, in many cities around the world.”

But, despite the limitations of an observational study and possible selection bias of people who are able to cycle, “it is important to share this evidence for the potentially large health benefits of cycling, which almost surely generalize to persons without diabetes.”
 

Cycling tied to lower all-cause and CVD mortality

The prospective cohort study included 7,459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition. All were assessed during 1992-1998 and again in 1996-2011, with a mean follow-up of roughly 15 years. During that time, there were 1,673 deaths from all causes, with 811 attributed to CVD.

Compared with no cycling, those who reported any cycling had a 24% lower risk of death from any cause over a 5-year period, after adjustment for confounders and for other physical activity. The greatest risk reduction was seen in those who reported cycling between 150-299 minutes per week, particularly in CVD mortality.

In a subanalysis of 5,423 individuals with 10.7 years of follow-up, there were 975 all-cause deaths and 429 from CVD. Individuals who began or continued cycling during follow-up experienced reductions of about 35% for both all-cause and CVD mortality, compared with those who never cycled.

Dr. Redberg and colleagues added that “there are environmental benefits to increasing the use of cycling for commuting and other transport because cycling helps to decrease the adverse environmental and health effects of automobile exhaust.”

They concluded: “As avid and/or aspiring cyclists ourselves, we are sold on the mental and physical benefits of getting to work and seeing the world on two wheels, self-propelled, and think it is well worth a try.”

The study work was supported by the Health Research Fund of Instituto de Salud Carlos III; the Spanish regional governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra; and the Catalan Institute of Oncology. The Centre for Physical Activity Research is supported by a grant from TrygFonden. Dr. Ried-Larsen reported personal fees from Novo Nordisk. Dr. Redberg reported receiving grants from Arnold Ventures; the Greenwall Foundation; and the National Heart, Lung, and Blood Institute.

Bicycle riding may help people with diabetes live longer, new research suggests.

NicolasMcComber/E+/Getty Images

Among more than 7,000 adults with diabetes in 10 Western European countries followed for about 15 years, those who cycled regularly were significantly less likely to die of any cause or of cardiovascular causes, even after accounting for differences in factors such as sex, age, educational level, diet, comorbidities, and other physical activities.

“The association between cycling and all-cause and CVD [cardiovascular disease] mortality in this study of person[s] with diabetes was of the same magnitude and direction as observed in the healthy population,” wrote Mathias Ried-Larsen, PhD, of the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and colleagues. The findings were published online July 19, 2021, in JAMA Internal Medicine.

In an accompanying Editor’s Note, JAMA Internal Medicine editor Rita F. Redberg, MD, and two deputy editors said that the new data add to previous studies showing benefits of cycling, compared with other physical activities. “The analysis from Ried-Larsen and colleagues strengthens the epidemiologic data on cycling and strongly suggests that it may contribute directly to longer and healthier lives,” they wrote.

Dr. Redberg, of the University of California, San Francisco, told this news organization: “I think the number of cyclists grew greatly during pandemic, when there was little auto traffic, and people did not want to take public transportation. Cities that add bike lanes, especially protected bike lanes, see an increase in cyclists. I think Americans can cycle more, would enjoy cycling more, and would live longer [by] cycling, to work and for pleasure.”

Dr. Redberg disclosed that she is “an avid cyclist and am currently on a bike ride in Glacier National Park. ... This group [Climate Ride] raises money for more bike lanes, promotes climate change awareness, has paid for solar panels at Glacier, and more.”

However, Dr. Redberg and colleagues also “recognize that cycling requires fitness, a good sense of balance, and the means to purchase a bicycle. We also understand that regular cycling requires living in an area where it is reasonably safe, and we celebrate the installation of more bike lanes, particularly protected lanes, in many cities around the world.”

But, despite the limitations of an observational study and possible selection bias of people who are able to cycle, “it is important to share this evidence for the potentially large health benefits of cycling, which almost surely generalize to persons without diabetes.”
 

Cycling tied to lower all-cause and CVD mortality

The prospective cohort study included 7,459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition. All were assessed during 1992-1998 and again in 1996-2011, with a mean follow-up of roughly 15 years. During that time, there were 1,673 deaths from all causes, with 811 attributed to CVD.

Compared with no cycling, those who reported any cycling had a 24% lower risk of death from any cause over a 5-year period, after adjustment for confounders and for other physical activity. The greatest risk reduction was seen in those who reported cycling between 150-299 minutes per week, particularly in CVD mortality.

In a subanalysis of 5,423 individuals with 10.7 years of follow-up, there were 975 all-cause deaths and 429 from CVD. Individuals who began or continued cycling during follow-up experienced reductions of about 35% for both all-cause and CVD mortality, compared with those who never cycled.

Dr. Redberg and colleagues added that “there are environmental benefits to increasing the use of cycling for commuting and other transport because cycling helps to decrease the adverse environmental and health effects of automobile exhaust.”

They concluded: “As avid and/or aspiring cyclists ourselves, we are sold on the mental and physical benefits of getting to work and seeing the world on two wheels, self-propelled, and think it is well worth a try.”

The study work was supported by the Health Research Fund of Instituto de Salud Carlos III; the Spanish regional governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra; and the Catalan Institute of Oncology. The Centre for Physical Activity Research is supported by a grant from TrygFonden. Dr. Ried-Larsen reported personal fees from Novo Nordisk. Dr. Redberg reported receiving grants from Arnold Ventures; the Greenwall Foundation; and the National Heart, Lung, and Blood Institute.

Bicycle riding may help people with diabetes live longer, new research suggests.

NicolasMcComber/E+/Getty Images

Among more than 7,000 adults with diabetes in 10 Western European countries followed for about 15 years, those who cycled regularly were significantly less likely to die of any cause or of cardiovascular causes, even after accounting for differences in factors such as sex, age, educational level, diet, comorbidities, and other physical activities.

“The association between cycling and all-cause and CVD [cardiovascular disease] mortality in this study of person[s] with diabetes was of the same magnitude and direction as observed in the healthy population,” wrote Mathias Ried-Larsen, PhD, of the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and colleagues. The findings were published online July 19, 2021, in JAMA Internal Medicine.

In an accompanying Editor’s Note, JAMA Internal Medicine editor Rita F. Redberg, MD, and two deputy editors said that the new data add to previous studies showing benefits of cycling, compared with other physical activities. “The analysis from Ried-Larsen and colleagues strengthens the epidemiologic data on cycling and strongly suggests that it may contribute directly to longer and healthier lives,” they wrote.

Dr. Redberg, of the University of California, San Francisco, told this news organization: “I think the number of cyclists grew greatly during pandemic, when there was little auto traffic, and people did not want to take public transportation. Cities that add bike lanes, especially protected bike lanes, see an increase in cyclists. I think Americans can cycle more, would enjoy cycling more, and would live longer [by] cycling, to work and for pleasure.”

Dr. Redberg disclosed that she is “an avid cyclist and am currently on a bike ride in Glacier National Park. ... This group [Climate Ride] raises money for more bike lanes, promotes climate change awareness, has paid for solar panels at Glacier, and more.”

However, Dr. Redberg and colleagues also “recognize that cycling requires fitness, a good sense of balance, and the means to purchase a bicycle. We also understand that regular cycling requires living in an area where it is reasonably safe, and we celebrate the installation of more bike lanes, particularly protected lanes, in many cities around the world.”

But, despite the limitations of an observational study and possible selection bias of people who are able to cycle, “it is important to share this evidence for the potentially large health benefits of cycling, which almost surely generalize to persons without diabetes.”
 

Cycling tied to lower all-cause and CVD mortality

The prospective cohort study included 7,459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition. All were assessed during 1992-1998 and again in 1996-2011, with a mean follow-up of roughly 15 years. During that time, there were 1,673 deaths from all causes, with 811 attributed to CVD.

Compared with no cycling, those who reported any cycling had a 24% lower risk of death from any cause over a 5-year period, after adjustment for confounders and for other physical activity. The greatest risk reduction was seen in those who reported cycling between 150-299 minutes per week, particularly in CVD mortality.

In a subanalysis of 5,423 individuals with 10.7 years of follow-up, there were 975 all-cause deaths and 429 from CVD. Individuals who began or continued cycling during follow-up experienced reductions of about 35% for both all-cause and CVD mortality, compared with those who never cycled.

Dr. Redberg and colleagues added that “there are environmental benefits to increasing the use of cycling for commuting and other transport because cycling helps to decrease the adverse environmental and health effects of automobile exhaust.”

They concluded: “As avid and/or aspiring cyclists ourselves, we are sold on the mental and physical benefits of getting to work and seeing the world on two wheels, self-propelled, and think it is well worth a try.”

The study work was supported by the Health Research Fund of Instituto de Salud Carlos III; the Spanish regional governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra; and the Catalan Institute of Oncology. The Centre for Physical Activity Research is supported by a grant from TrygFonden. Dr. Ried-Larsen reported personal fees from Novo Nordisk. Dr. Redberg reported receiving grants from Arnold Ventures; the Greenwall Foundation; and the National Heart, Lung, and Blood Institute.

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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