Federal Practitioner

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

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

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

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

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

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

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we’re going to talk about the consensus report by the American Diabetes Association and the European Association for the Study of Diabetes on the management of hyperglycemia.

A lot has changed in this consensus statement. It covers a lot of ground. We’re going to focus today on pharmacologic management.

After lifestyle modifications, metformin is no longer the go-to drug for every patient in the management of hyperglycemia. It is recommended that we assess each patient’s personal characteristics in deciding what medication to prescribe. For patients at high cardiorenal risk, refer to the left side of the algorithm and to the right side for all other patients.

American Diabetes Association

• Very high efficacy for glucose lowering: dulaglutide at a high dose, semaglutide, tirzepatide, insulin, or combination injectable agents (GLP-1 receptor agonist/insulin combinations).
• High glucose-lowering efficacy: a GLP-1 receptor agonist not already mentioned, metformin, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones.
• Intermediate glucose lowering efficacy: dipeptidyl peptidase 4 (DPP-4) inhibitors.

Weight management. For weight management, lifestyle modification (diet and exercise) is important. If lifestyle modification alone is insufficient, consider either a medication that specifically helps with weight management or metabolic surgery.

We particularly want to focus on weight management in patients who have complications from obesity. What would those complications be? Sleep apnea, hip or knee pain from arthritis, back pain – that is, biomechanical complications of obesity or nonalcoholic fatty liver disease. Medications for weight loss are listed by degree of efficacy:

• Very high efficacy for weight loss: semaglutide, tirzepatide.
• High efficacy for weight loss: dulaglutide and liraglutide.
• Intermediate for weight loss: GLP-1 receptor agonist (not listed above), SGLT-2 inhibitor.
• Neutral for weight loss: DPP-4 inhibitors and metformin.

Where does insulin fit in? If patients present with a very high A1c, if they are on other medications and their A1c is still not to goal, or if they are catabolic and losing weight because of their diabetes, then insulin has an important place in management.

These are incredibly important guidelines that provide a clear algorithm for a personalized approach to diabetes management.
 

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He reported conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we’re going to talk about the consensus report by the American Diabetes Association and the European Association for the Study of Diabetes on the management of hyperglycemia.

A lot has changed in this consensus statement. It covers a lot of ground. We’re going to focus today on pharmacologic management.

After lifestyle modifications, metformin is no longer the go-to drug for every patient in the management of hyperglycemia. It is recommended that we assess each patient’s personal characteristics in deciding what medication to prescribe. For patients at high cardiorenal risk, refer to the left side of the algorithm and to the right side for all other patients.

American Diabetes Association

• Very high efficacy for glucose lowering: dulaglutide at a high dose, semaglutide, tirzepatide, insulin, or combination injectable agents (GLP-1 receptor agonist/insulin combinations).
• High glucose-lowering efficacy: a GLP-1 receptor agonist not already mentioned, metformin, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones.
• Intermediate glucose lowering efficacy: dipeptidyl peptidase 4 (DPP-4) inhibitors.

Weight management. For weight management, lifestyle modification (diet and exercise) is important. If lifestyle modification alone is insufficient, consider either a medication that specifically helps with weight management or metabolic surgery.

We particularly want to focus on weight management in patients who have complications from obesity. What would those complications be? Sleep apnea, hip or knee pain from arthritis, back pain – that is, biomechanical complications of obesity or nonalcoholic fatty liver disease. Medications for weight loss are listed by degree of efficacy:

• Very high efficacy for weight loss: semaglutide, tirzepatide.
• High efficacy for weight loss: dulaglutide and liraglutide.
• Intermediate for weight loss: GLP-1 receptor agonist (not listed above), SGLT-2 inhibitor.
• Neutral for weight loss: DPP-4 inhibitors and metformin.

Where does insulin fit in? If patients present with a very high A1c, if they are on other medications and their A1c is still not to goal, or if they are catabolic and losing weight because of their diabetes, then insulin has an important place in management.

These are incredibly important guidelines that provide a clear algorithm for a personalized approach to diabetes management.
 

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He reported conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we’re going to talk about the consensus report by the American Diabetes Association and the European Association for the Study of Diabetes on the management of hyperglycemia.

A lot has changed in this consensus statement. It covers a lot of ground. We’re going to focus today on pharmacologic management.

After lifestyle modifications, metformin is no longer the go-to drug for every patient in the management of hyperglycemia. It is recommended that we assess each patient’s personal characteristics in deciding what medication to prescribe. For patients at high cardiorenal risk, refer to the left side of the algorithm and to the right side for all other patients.

American Diabetes Association

• Very high efficacy for glucose lowering: dulaglutide at a high dose, semaglutide, tirzepatide, insulin, or combination injectable agents (GLP-1 receptor agonist/insulin combinations).
• High glucose-lowering efficacy: a GLP-1 receptor agonist not already mentioned, metformin, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones.
• Intermediate glucose lowering efficacy: dipeptidyl peptidase 4 (DPP-4) inhibitors.

Weight management. For weight management, lifestyle modification (diet and exercise) is important. If lifestyle modification alone is insufficient, consider either a medication that specifically helps with weight management or metabolic surgery.

We particularly want to focus on weight management in patients who have complications from obesity. What would those complications be? Sleep apnea, hip or knee pain from arthritis, back pain – that is, biomechanical complications of obesity or nonalcoholic fatty liver disease. Medications for weight loss are listed by degree of efficacy:

• Very high efficacy for weight loss: semaglutide, tirzepatide.
• High efficacy for weight loss: dulaglutide and liraglutide.
• Intermediate for weight loss: GLP-1 receptor agonist (not listed above), SGLT-2 inhibitor.
• Neutral for weight loss: DPP-4 inhibitors and metformin.

Where does insulin fit in? If patients present with a very high A1c, if they are on other medications and their A1c is still not to goal, or if they are catabolic and losing weight because of their diabetes, then insulin has an important place in management.

These are incredibly important guidelines that provide a clear algorithm for a personalized approach to diabetes management.
 

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He reported conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. A version of this article first appeared on Medscape.com.

Mindfulness-based stress reduction (MBSR) is as effective at reducing anxiety as the antidepressant escitalopram, a first-line pharmaceutical treatment, new research shows.

“I would encourage clinicians to list meditation training as one possible treatment option for patients who are diagnosed with anxiety disorders. Doctors should feel comfortable recommending in-person, group-based meditation classes,” study investigator Elizabeth A. Hoge, MD, director, Anxiety Disorders Research Program, Georgetown University Medical Center, Washington, told this news organization.

The findings were published online  in JAMA Psychiatry.
 

Screening recommended

Anxiety disorders, including generalized anxiety, social anxiety, panic disorder, and agoraphobia, are the most common type of mental disorder, affecting an estimated 301 million people worldwide. Owing to their high prevalence, the United States Preventive Services Task Force recommends screening for anxiety disorders.

Effective treatments for anxiety disorders include medications and cognitive-behavioral therapy. However, not all patients have access to these interventions, respond to them, or are comfortable seeking care in a psychiatric setting.

Mindfulness meditation, which has risen in popularity in recent years, may help people experiencing intrusive, anxious thoughts. “By practicing mindfulness meditation, people learn not to be overwhelmed by those thoughts,” said Dr. Hoge.

The study included 276 adult patients with an anxiety disorder, mostly generalized anxiety or social anxiety. The mean age of the study population was 33 years; 75% were women, 59% were White, 15% were Black, and 20% were Asian.

Researchers randomly assigned 136 patients to receive MBSR and 140 to receive the selective serotonin reuptake inhibitor escitalopram, a first-line medication for treating anxiety disorders.

The MBSR intervention included a weekly 2.5-hour class and a day-long weekend class. Participants also completed daily 45-minute guided meditation sessions at home. They learned mindfulness meditation exercises, including breath awareness, body scanning, and mindful movement.

Those in the escitalopram group initially received 10 mg of the oral drug daily. The dose was increased to 20 mg daily at week 2 if well tolerated.

The primary outcome was the score on the Clinical Global Impression of Severity (CGI-S) scale for anxiety, assessed by clinicians blinded to treatment allocation. This instrument measures overall symptom severity on a scale from 1 (not at all ill) to 7 (most extremely ill) and can be used to assess different types of anxiety disorders, said Dr. Hoge.

Among the 208 participants who completed the study, the baseline mean CGI-S score was 4.44 for MBSR and 4.51 for escitalopram. At week 8, on the CGI-S scale, the MBSR group’s score improved by a mean of 1.35 points, and the escitalopram group’s score improved by 1.43 points (difference of –0.07; 95% CI, –0.38 to 0.23; P = .65).

The lower end of the confidence interval (–0.38) was smaller than the prespecified noninferiority margin of –0.495, indicating noninferiority of MBSR, compared with escitalopram.
 

Remarkable results

“What was remarkable was that the medication worked great, like it always does, but the meditation also worked great; we saw about a 30% drop in symptoms for both groups,” said Dr. Hoge. “That helps us know that meditation, and in particular mindfulness meditation, could be useful as a first-line treatment for patients with anxiety disorders.”

The patient-reported outcome of the Overall Anxiety Severity and Impairment Scale also showed no significant group differences. “It’s important to have the self-reports, because that gives us two ways to look at the information,” said Dr. Hoge.

Anecdotally, participants noted that the meditation helped with their personal relationships and with being “kinder to themselves,” said Dr. Hoge. “In meditation, there’s an implicit teaching to be accepting and nonjudgmental towards your own thoughts, and that teaches people to be more self-compassionate.”

Just over 78% of patients in the escitalopram group had at least one treatment-related adverse event (AE), which included sleep disturbances, nausea, fatigue, and headache, compared with 15.4% in the MBSR group.

The most common AE in the meditation group was anxiety, which is “counterintuitive” but represents “a momentary anxiety,” said Dr. Hoge. “People who are meditating have feelings come up that maybe they didn’t pay attention to before. This gives them an opportunity to process through those emotions.”

Fatigue was the next most common AE for meditators, which “makes sense,” since they’re putting away their phones and not being stimulated, said Dr. Hoge.

MBSR was delivered in person, which limits extrapolation to mindfulness apps or programs delivered over the internet. Dr. Hoge believes apps would likely be less effective because they don’t have the face-to-face component, instructors available for consultation, or fellow participants contributing group support.

But online classes might work if “the exact same class,” including all its components, is moved online, she said.

MBSR is available in all major U.S. cities, doesn’t require finding a therapist, and is available outside a mental health environment – for example, at yoga centers and some places of employment. Anyone can learn MBSR, although it takes time and commitment, said Dr. Hoge.
 

A time-tested intervention

Commenting on the study, psychiatrist Gregory Scott Brown, MD, affiliate faculty, University of Texas Dell Medical School, and author of “The Self-Healing Mind: An Essential Five-Step Practice for Overcoming Anxiety and Depression and Revitalizing Your Life,” said the results aren’t surprising inasmuch as mindfulness, including spirituality, breath work, and meditation, is a “time-tested and evidence-based” intervention.

“I’m encouraged by the fact studies like this are now being conducted and there’s more evidence that supports these mindfulness-based interventions, so they can start to make their way into standard-of-care treatments.” he said.

He noted that mindfulness can produce “long-term, sustainable improvements” and that the 45-minute daily home exercise included in the study “is not a huge time commitment when you talk about benefits you can potentially glean from incorporating that time.”

Because most study participants were women and “men are anxious too,” Dr. Brown said he would like to see the study replicated “with a more diverse pool of participants.”

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Hoge and Dr. Brown have reported no relevant financial relationships.

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

Mindfulness-based stress reduction (MBSR) is as effective at reducing anxiety as the antidepressant escitalopram, a first-line pharmaceutical treatment, new research shows.

“I would encourage clinicians to list meditation training as one possible treatment option for patients who are diagnosed with anxiety disorders. Doctors should feel comfortable recommending in-person, group-based meditation classes,” study investigator Elizabeth A. Hoge, MD, director, Anxiety Disorders Research Program, Georgetown University Medical Center, Washington, told this news organization.

The findings were published online  in JAMA Psychiatry.
 

Screening recommended

Anxiety disorders, including generalized anxiety, social anxiety, panic disorder, and agoraphobia, are the most common type of mental disorder, affecting an estimated 301 million people worldwide. Owing to their high prevalence, the United States Preventive Services Task Force recommends screening for anxiety disorders.

Effective treatments for anxiety disorders include medications and cognitive-behavioral therapy. However, not all patients have access to these interventions, respond to them, or are comfortable seeking care in a psychiatric setting.

Mindfulness meditation, which has risen in popularity in recent years, may help people experiencing intrusive, anxious thoughts. “By practicing mindfulness meditation, people learn not to be overwhelmed by those thoughts,” said Dr. Hoge.

The study included 276 adult patients with an anxiety disorder, mostly generalized anxiety or social anxiety. The mean age of the study population was 33 years; 75% were women, 59% were White, 15% were Black, and 20% were Asian.

Researchers randomly assigned 136 patients to receive MBSR and 140 to receive the selective serotonin reuptake inhibitor escitalopram, a first-line medication for treating anxiety disorders.

The MBSR intervention included a weekly 2.5-hour class and a day-long weekend class. Participants also completed daily 45-minute guided meditation sessions at home. They learned mindfulness meditation exercises, including breath awareness, body scanning, and mindful movement.

Those in the escitalopram group initially received 10 mg of the oral drug daily. The dose was increased to 20 mg daily at week 2 if well tolerated.

The primary outcome was the score on the Clinical Global Impression of Severity (CGI-S) scale for anxiety, assessed by clinicians blinded to treatment allocation. This instrument measures overall symptom severity on a scale from 1 (not at all ill) to 7 (most extremely ill) and can be used to assess different types of anxiety disorders, said Dr. Hoge.

Among the 208 participants who completed the study, the baseline mean CGI-S score was 4.44 for MBSR and 4.51 for escitalopram. At week 8, on the CGI-S scale, the MBSR group’s score improved by a mean of 1.35 points, and the escitalopram group’s score improved by 1.43 points (difference of –0.07; 95% CI, –0.38 to 0.23; P = .65).

The lower end of the confidence interval (–0.38) was smaller than the prespecified noninferiority margin of –0.495, indicating noninferiority of MBSR, compared with escitalopram.
 

Remarkable results

“What was remarkable was that the medication worked great, like it always does, but the meditation also worked great; we saw about a 30% drop in symptoms for both groups,” said Dr. Hoge. “That helps us know that meditation, and in particular mindfulness meditation, could be useful as a first-line treatment for patients with anxiety disorders.”

The patient-reported outcome of the Overall Anxiety Severity and Impairment Scale also showed no significant group differences. “It’s important to have the self-reports, because that gives us two ways to look at the information,” said Dr. Hoge.

Anecdotally, participants noted that the meditation helped with their personal relationships and with being “kinder to themselves,” said Dr. Hoge. “In meditation, there’s an implicit teaching to be accepting and nonjudgmental towards your own thoughts, and that teaches people to be more self-compassionate.”

Just over 78% of patients in the escitalopram group had at least one treatment-related adverse event (AE), which included sleep disturbances, nausea, fatigue, and headache, compared with 15.4% in the MBSR group.

The most common AE in the meditation group was anxiety, which is “counterintuitive” but represents “a momentary anxiety,” said Dr. Hoge. “People who are meditating have feelings come up that maybe they didn’t pay attention to before. This gives them an opportunity to process through those emotions.”

Fatigue was the next most common AE for meditators, which “makes sense,” since they’re putting away their phones and not being stimulated, said Dr. Hoge.

MBSR was delivered in person, which limits extrapolation to mindfulness apps or programs delivered over the internet. Dr. Hoge believes apps would likely be less effective because they don’t have the face-to-face component, instructors available for consultation, or fellow participants contributing group support.

But online classes might work if “the exact same class,” including all its components, is moved online, she said.

MBSR is available in all major U.S. cities, doesn’t require finding a therapist, and is available outside a mental health environment – for example, at yoga centers and some places of employment. Anyone can learn MBSR, although it takes time and commitment, said Dr. Hoge.
 

A time-tested intervention

Commenting on the study, psychiatrist Gregory Scott Brown, MD, affiliate faculty, University of Texas Dell Medical School, and author of “The Self-Healing Mind: An Essential Five-Step Practice for Overcoming Anxiety and Depression and Revitalizing Your Life,” said the results aren’t surprising inasmuch as mindfulness, including spirituality, breath work, and meditation, is a “time-tested and evidence-based” intervention.

“I’m encouraged by the fact studies like this are now being conducted and there’s more evidence that supports these mindfulness-based interventions, so they can start to make their way into standard-of-care treatments.” he said.

He noted that mindfulness can produce “long-term, sustainable improvements” and that the 45-minute daily home exercise included in the study “is not a huge time commitment when you talk about benefits you can potentially glean from incorporating that time.”

Because most study participants were women and “men are anxious too,” Dr. Brown said he would like to see the study replicated “with a more diverse pool of participants.”

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Hoge and Dr. Brown have reported no relevant financial relationships.

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

Mindfulness-based stress reduction (MBSR) is as effective at reducing anxiety as the antidepressant escitalopram, a first-line pharmaceutical treatment, new research shows.

“I would encourage clinicians to list meditation training as one possible treatment option for patients who are diagnosed with anxiety disorders. Doctors should feel comfortable recommending in-person, group-based meditation classes,” study investigator Elizabeth A. Hoge, MD, director, Anxiety Disorders Research Program, Georgetown University Medical Center, Washington, told this news organization.

The findings were published online  in JAMA Psychiatry.
 

Screening recommended

Anxiety disorders, including generalized anxiety, social anxiety, panic disorder, and agoraphobia, are the most common type of mental disorder, affecting an estimated 301 million people worldwide. Owing to their high prevalence, the United States Preventive Services Task Force recommends screening for anxiety disorders.

Effective treatments for anxiety disorders include medications and cognitive-behavioral therapy. However, not all patients have access to these interventions, respond to them, or are comfortable seeking care in a psychiatric setting.

Mindfulness meditation, which has risen in popularity in recent years, may help people experiencing intrusive, anxious thoughts. “By practicing mindfulness meditation, people learn not to be overwhelmed by those thoughts,” said Dr. Hoge.

The study included 276 adult patients with an anxiety disorder, mostly generalized anxiety or social anxiety. The mean age of the study population was 33 years; 75% were women, 59% were White, 15% were Black, and 20% were Asian.

Researchers randomly assigned 136 patients to receive MBSR and 140 to receive the selective serotonin reuptake inhibitor escitalopram, a first-line medication for treating anxiety disorders.

The MBSR intervention included a weekly 2.5-hour class and a day-long weekend class. Participants also completed daily 45-minute guided meditation sessions at home. They learned mindfulness meditation exercises, including breath awareness, body scanning, and mindful movement.

Those in the escitalopram group initially received 10 mg of the oral drug daily. The dose was increased to 20 mg daily at week 2 if well tolerated.

The primary outcome was the score on the Clinical Global Impression of Severity (CGI-S) scale for anxiety, assessed by clinicians blinded to treatment allocation. This instrument measures overall symptom severity on a scale from 1 (not at all ill) to 7 (most extremely ill) and can be used to assess different types of anxiety disorders, said Dr. Hoge.

Among the 208 participants who completed the study, the baseline mean CGI-S score was 4.44 for MBSR and 4.51 for escitalopram. At week 8, on the CGI-S scale, the MBSR group’s score improved by a mean of 1.35 points, and the escitalopram group’s score improved by 1.43 points (difference of –0.07; 95% CI, –0.38 to 0.23; P = .65).

The lower end of the confidence interval (–0.38) was smaller than the prespecified noninferiority margin of –0.495, indicating noninferiority of MBSR, compared with escitalopram.
 

Remarkable results

“What was remarkable was that the medication worked great, like it always does, but the meditation also worked great; we saw about a 30% drop in symptoms for both groups,” said Dr. Hoge. “That helps us know that meditation, and in particular mindfulness meditation, could be useful as a first-line treatment for patients with anxiety disorders.”

The patient-reported outcome of the Overall Anxiety Severity and Impairment Scale also showed no significant group differences. “It’s important to have the self-reports, because that gives us two ways to look at the information,” said Dr. Hoge.

Anecdotally, participants noted that the meditation helped with their personal relationships and with being “kinder to themselves,” said Dr. Hoge. “In meditation, there’s an implicit teaching to be accepting and nonjudgmental towards your own thoughts, and that teaches people to be more self-compassionate.”

Just over 78% of patients in the escitalopram group had at least one treatment-related adverse event (AE), which included sleep disturbances, nausea, fatigue, and headache, compared with 15.4% in the MBSR group.

The most common AE in the meditation group was anxiety, which is “counterintuitive” but represents “a momentary anxiety,” said Dr. Hoge. “People who are meditating have feelings come up that maybe they didn’t pay attention to before. This gives them an opportunity to process through those emotions.”

Fatigue was the next most common AE for meditators, which “makes sense,” since they’re putting away their phones and not being stimulated, said Dr. Hoge.

MBSR was delivered in person, which limits extrapolation to mindfulness apps or programs delivered over the internet. Dr. Hoge believes apps would likely be less effective because they don’t have the face-to-face component, instructors available for consultation, or fellow participants contributing group support.

But online classes might work if “the exact same class,” including all its components, is moved online, she said.

MBSR is available in all major U.S. cities, doesn’t require finding a therapist, and is available outside a mental health environment – for example, at yoga centers and some places of employment. Anyone can learn MBSR, although it takes time and commitment, said Dr. Hoge.
 

A time-tested intervention

Commenting on the study, psychiatrist Gregory Scott Brown, MD, affiliate faculty, University of Texas Dell Medical School, and author of “The Self-Healing Mind: An Essential Five-Step Practice for Overcoming Anxiety and Depression and Revitalizing Your Life,” said the results aren’t surprising inasmuch as mindfulness, including spirituality, breath work, and meditation, is a “time-tested and evidence-based” intervention.

“I’m encouraged by the fact studies like this are now being conducted and there’s more evidence that supports these mindfulness-based interventions, so they can start to make their way into standard-of-care treatments.” he said.

He noted that mindfulness can produce “long-term, sustainable improvements” and that the 45-minute daily home exercise included in the study “is not a huge time commitment when you talk about benefits you can potentially glean from incorporating that time.”

Because most study participants were women and “men are anxious too,” Dr. Brown said he would like to see the study replicated “with a more diverse pool of participants.”

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Hoge and Dr. Brown have reported no relevant financial relationships.

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

ORLANDO – Hospitalization rates were higher in patients with advanced chronic kidney disease (CKD) treated with dialysis than those treated with conservative management, among those with an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m² and in most racial/ethnic groups, new research shows.

“Patients mostly start dialysis because of unpleasant symptoms that cause suffering, including high potassium levels and high levels of uremic toxins in the blood,” senior author Kamyar Kalantar-Zadeh, MD, PhD, MPH, told this news organization.

“Conservative management serves to address and manage these symptoms and levels of toxicities without dialysis, so conservative management is an alternative approach, and patients should always be given a choice between [the two],” stressed Dr. Kalantar-Zadeh, professor of medicine at the University of California, Irvine.

The results were presented during the annual meeting of the American Society of Nephrology.

“There has been growing recognition of the importance of conservative nondialytic management as an alternative patient-centered treatment strategy for advanced kidney disease. However, conservative management remains under-utilized in the United States, which may in part be due to uncertainties regarding which patients will most benefit from dialysis versus nondialytic treatment,” said first author Connie Rhee, MD, also of the University of California, Irvine.

“We hope that these findings and further research can help inform treatment options for patients, care partners, and providers in the shared decision-making process of conservative management versus dialysis,” added Dr. Rhee, in a press release from the American Society of Nephrology.

Asked for comment, Sarah Davison, MD, noted that part of the Society’s strategy is, in fact, to promote conservative kidney management (CKM) as a key component of integrated care for patients with kidney failure. Dr. Davison is professor of medicine and chair of the International Society Working Group for Kidney Supportive Care and Conservative Kidney Management.

“We’ve recognized for a long time that there are many patients for whom dialysis provides neither a survival advantage nor a quality of life advantage,” she told this news organization.

“These patients tend to be those who have multiple morbidities, who are more frail, and who tend to be older, and in fact, the patients can live as long, if not longer, with better symptom management and better quality of life by not being on dialysis,” she stressed.
 

Study details

In the study, using data from the Optum Labs Data Warehouse, patients with advanced CKD were categorized according to whether or not they received conservative management, defined as those who did not receive dialysis within 2 years of the index eGFR (first eGFR < 25 mL/min/1.73m²) versus receipt of dialysis parsed as late versus early dialysis transition (eGFR < 15 vs. ≥ 15 mL/min/1.73m² at dialysis initiation).

Hospitalization rates were compared between those treated with conservative management, compared with late or early dialysis.

“Among 309,188 advanced CKD patients who met eligibility [criteria], 55% of patients had greater than or equal to 1 hospitalization(s) within 2 years of the index eGFR,” the authors report. The most common causes of hospitalization among all patients were congestive heart failure, respiratory symptoms, or hypertension.

In most racial groups (non-Hispanic White, non-Hispanic Black, and Hispanic patients), patients on dialysis had higher hospitalization rates than those who received conservative management, and patients who started dialysis early (transitioned to dialysis at higher levels of kidney function) demonstrated the highest rates across all age groups, compared with those who started dialysis late (transitioned to dialysis at lower levels of kidney function) or were treated with conservative management.

Among Asian patients, those on dialysis also had higher hospitalization rates than those receiving conservative management, but patients who started dialysis late had higher rates than those on early dialysis, especially in older age groups, possibly because they were sicker, Dr. Kalantar-Zadeh suggested.
 

Conservative care has pros and cons, but Canada has embraced it

As Dr. Kalantar-Zadeh explained, conservative management has its pros and cons, compared with dialysis. “Conservative management requires that patients work with the multidisciplinary team including nephrologists, nutritionists, and others to try to manage CKD without dialysis, so it requires patient participation.”

On the other hand, dialysis is both easier and more lucrative than conservative management, at least for nephrologists, as they are well-trained in dialysis care, and it can be systematically applied. As to which patients with CKD might be optimal candidates for conservative management, Dr. Kalantar-Zadeh agreed this requires further study.

But he acknowledged that most nephrologists are not hugely supportive of conservative management because they are less well-trained in it, and it is more time-consuming. The one promising change is a new model introduced in 2022, a value-based kidney care model, that, if implemented, will be more incentivizing for nephrologists to offer conservative care more widely.

Dr. Davison meanwhile believes the “vast majority” of nephrologists based in Canada – as she is – are “highly supportive” of CKM as an important modality.

“The challenge, however, is that many nephrologists remain unsure as to how to best deliver or optimize all aspects of CKM, whether that is symptom management, advanced care planning, or how they must manage symptoms to align with a patient’s goals,” Dr. Davison explained.

“But it’s not that they do not believe in the value of CKM.”

Indeed, in her province, Alberta, nephrologists have been offering CKM for decades, and while they are currently standardizing care to make it easier to deliver, there is no financial incentive to offer dialysis over CKM.

“We are now seeing those elements of kidney supportive care as part of core competencies to manage any person with chronic illness, including CKD,” Dr. Davison said.

“So it’s absolutely doable, and contrary to one of the myths about CKM, it is not more time-consuming than dialysis – not when you know how to do it. You are just shifting your focus,” she emphasized.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Kalantar-Zadeh has reported receiving honoraria and medical directorship fees from Fresenius and DaVita. Dr. Davison has reported no relevant financial relationships.

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

ORLANDO – Hospitalization rates were higher in patients with advanced chronic kidney disease (CKD) treated with dialysis than those treated with conservative management, among those with an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m² and in most racial/ethnic groups, new research shows.

“Patients mostly start dialysis because of unpleasant symptoms that cause suffering, including high potassium levels and high levels of uremic toxins in the blood,” senior author Kamyar Kalantar-Zadeh, MD, PhD, MPH, told this news organization.

“Conservative management serves to address and manage these symptoms and levels of toxicities without dialysis, so conservative management is an alternative approach, and patients should always be given a choice between [the two],” stressed Dr. Kalantar-Zadeh, professor of medicine at the University of California, Irvine.

The results were presented during the annual meeting of the American Society of Nephrology.

“There has been growing recognition of the importance of conservative nondialytic management as an alternative patient-centered treatment strategy for advanced kidney disease. However, conservative management remains under-utilized in the United States, which may in part be due to uncertainties regarding which patients will most benefit from dialysis versus nondialytic treatment,” said first author Connie Rhee, MD, also of the University of California, Irvine.

“We hope that these findings and further research can help inform treatment options for patients, care partners, and providers in the shared decision-making process of conservative management versus dialysis,” added Dr. Rhee, in a press release from the American Society of Nephrology.

Asked for comment, Sarah Davison, MD, noted that part of the Society’s strategy is, in fact, to promote conservative kidney management (CKM) as a key component of integrated care for patients with kidney failure. Dr. Davison is professor of medicine and chair of the International Society Working Group for Kidney Supportive Care and Conservative Kidney Management.

“We’ve recognized for a long time that there are many patients for whom dialysis provides neither a survival advantage nor a quality of life advantage,” she told this news organization.

“These patients tend to be those who have multiple morbidities, who are more frail, and who tend to be older, and in fact, the patients can live as long, if not longer, with better symptom management and better quality of life by not being on dialysis,” she stressed.
 

Study details

In the study, using data from the Optum Labs Data Warehouse, patients with advanced CKD were categorized according to whether or not they received conservative management, defined as those who did not receive dialysis within 2 years of the index eGFR (first eGFR < 25 mL/min/1.73m²) versus receipt of dialysis parsed as late versus early dialysis transition (eGFR < 15 vs. ≥ 15 mL/min/1.73m² at dialysis initiation).

Hospitalization rates were compared between those treated with conservative management, compared with late or early dialysis.

“Among 309,188 advanced CKD patients who met eligibility [criteria], 55% of patients had greater than or equal to 1 hospitalization(s) within 2 years of the index eGFR,” the authors report. The most common causes of hospitalization among all patients were congestive heart failure, respiratory symptoms, or hypertension.

In most racial groups (non-Hispanic White, non-Hispanic Black, and Hispanic patients), patients on dialysis had higher hospitalization rates than those who received conservative management, and patients who started dialysis early (transitioned to dialysis at higher levels of kidney function) demonstrated the highest rates across all age groups, compared with those who started dialysis late (transitioned to dialysis at lower levels of kidney function) or were treated with conservative management.

Among Asian patients, those on dialysis also had higher hospitalization rates than those receiving conservative management, but patients who started dialysis late had higher rates than those on early dialysis, especially in older age groups, possibly because they were sicker, Dr. Kalantar-Zadeh suggested.
 

Conservative care has pros and cons, but Canada has embraced it

As Dr. Kalantar-Zadeh explained, conservative management has its pros and cons, compared with dialysis. “Conservative management requires that patients work with the multidisciplinary team including nephrologists, nutritionists, and others to try to manage CKD without dialysis, so it requires patient participation.”

On the other hand, dialysis is both easier and more lucrative than conservative management, at least for nephrologists, as they are well-trained in dialysis care, and it can be systematically applied. As to which patients with CKD might be optimal candidates for conservative management, Dr. Kalantar-Zadeh agreed this requires further study.

But he acknowledged that most nephrologists are not hugely supportive of conservative management because they are less well-trained in it, and it is more time-consuming. The one promising change is a new model introduced in 2022, a value-based kidney care model, that, if implemented, will be more incentivizing for nephrologists to offer conservative care more widely.

Dr. Davison meanwhile believes the “vast majority” of nephrologists based in Canada – as she is – are “highly supportive” of CKM as an important modality.

“The challenge, however, is that many nephrologists remain unsure as to how to best deliver or optimize all aspects of CKM, whether that is symptom management, advanced care planning, or how they must manage symptoms to align with a patient’s goals,” Dr. Davison explained.

“But it’s not that they do not believe in the value of CKM.”

Indeed, in her province, Alberta, nephrologists have been offering CKM for decades, and while they are currently standardizing care to make it easier to deliver, there is no financial incentive to offer dialysis over CKM.

“We are now seeing those elements of kidney supportive care as part of core competencies to manage any person with chronic illness, including CKD,” Dr. Davison said.

“So it’s absolutely doable, and contrary to one of the myths about CKM, it is not more time-consuming than dialysis – not when you know how to do it. You are just shifting your focus,” she emphasized.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Kalantar-Zadeh has reported receiving honoraria and medical directorship fees from Fresenius and DaVita. Dr. Davison has reported no relevant financial relationships.

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

ORLANDO – Hospitalization rates were higher in patients with advanced chronic kidney disease (CKD) treated with dialysis than those treated with conservative management, among those with an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m² and in most racial/ethnic groups, new research shows.

“Patients mostly start dialysis because of unpleasant symptoms that cause suffering, including high potassium levels and high levels of uremic toxins in the blood,” senior author Kamyar Kalantar-Zadeh, MD, PhD, MPH, told this news organization.

“Conservative management serves to address and manage these symptoms and levels of toxicities without dialysis, so conservative management is an alternative approach, and patients should always be given a choice between [the two],” stressed Dr. Kalantar-Zadeh, professor of medicine at the University of California, Irvine.

The results were presented during the annual meeting of the American Society of Nephrology.

“There has been growing recognition of the importance of conservative nondialytic management as an alternative patient-centered treatment strategy for advanced kidney disease. However, conservative management remains under-utilized in the United States, which may in part be due to uncertainties regarding which patients will most benefit from dialysis versus nondialytic treatment,” said first author Connie Rhee, MD, also of the University of California, Irvine.

“We hope that these findings and further research can help inform treatment options for patients, care partners, and providers in the shared decision-making process of conservative management versus dialysis,” added Dr. Rhee, in a press release from the American Society of Nephrology.

Asked for comment, Sarah Davison, MD, noted that part of the Society’s strategy is, in fact, to promote conservative kidney management (CKM) as a key component of integrated care for patients with kidney failure. Dr. Davison is professor of medicine and chair of the International Society Working Group for Kidney Supportive Care and Conservative Kidney Management.

“We’ve recognized for a long time that there are many patients for whom dialysis provides neither a survival advantage nor a quality of life advantage,” she told this news organization.

“These patients tend to be those who have multiple morbidities, who are more frail, and who tend to be older, and in fact, the patients can live as long, if not longer, with better symptom management and better quality of life by not being on dialysis,” she stressed.
 

Study details

In the study, using data from the Optum Labs Data Warehouse, patients with advanced CKD were categorized according to whether or not they received conservative management, defined as those who did not receive dialysis within 2 years of the index eGFR (first eGFR < 25 mL/min/1.73m²) versus receipt of dialysis parsed as late versus early dialysis transition (eGFR < 15 vs. ≥ 15 mL/min/1.73m² at dialysis initiation).

Hospitalization rates were compared between those treated with conservative management, compared with late or early dialysis.

“Among 309,188 advanced CKD patients who met eligibility [criteria], 55% of patients had greater than or equal to 1 hospitalization(s) within 2 years of the index eGFR,” the authors report. The most common causes of hospitalization among all patients were congestive heart failure, respiratory symptoms, or hypertension.

In most racial groups (non-Hispanic White, non-Hispanic Black, and Hispanic patients), patients on dialysis had higher hospitalization rates than those who received conservative management, and patients who started dialysis early (transitioned to dialysis at higher levels of kidney function) demonstrated the highest rates across all age groups, compared with those who started dialysis late (transitioned to dialysis at lower levels of kidney function) or were treated with conservative management.

Among Asian patients, those on dialysis also had higher hospitalization rates than those receiving conservative management, but patients who started dialysis late had higher rates than those on early dialysis, especially in older age groups, possibly because they were sicker, Dr. Kalantar-Zadeh suggested.
 

Conservative care has pros and cons, but Canada has embraced it

As Dr. Kalantar-Zadeh explained, conservative management has its pros and cons, compared with dialysis. “Conservative management requires that patients work with the multidisciplinary team including nephrologists, nutritionists, and others to try to manage CKD without dialysis, so it requires patient participation.”

On the other hand, dialysis is both easier and more lucrative than conservative management, at least for nephrologists, as they are well-trained in dialysis care, and it can be systematically applied. As to which patients with CKD might be optimal candidates for conservative management, Dr. Kalantar-Zadeh agreed this requires further study.

But he acknowledged that most nephrologists are not hugely supportive of conservative management because they are less well-trained in it, and it is more time-consuming. The one promising change is a new model introduced in 2022, a value-based kidney care model, that, if implemented, will be more incentivizing for nephrologists to offer conservative care more widely.

Dr. Davison meanwhile believes the “vast majority” of nephrologists based in Canada – as she is – are “highly supportive” of CKM as an important modality.

“The challenge, however, is that many nephrologists remain unsure as to how to best deliver or optimize all aspects of CKM, whether that is symptom management, advanced care planning, or how they must manage symptoms to align with a patient’s goals,” Dr. Davison explained.

“But it’s not that they do not believe in the value of CKM.”

Indeed, in her province, Alberta, nephrologists have been offering CKM for decades, and while they are currently standardizing care to make it easier to deliver, there is no financial incentive to offer dialysis over CKM.

“We are now seeing those elements of kidney supportive care as part of core competencies to manage any person with chronic illness, including CKD,” Dr. Davison said.

“So it’s absolutely doable, and contrary to one of the myths about CKM, it is not more time-consuming than dialysis – not when you know how to do it. You are just shifting your focus,” she emphasized.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Kalantar-Zadeh has reported receiving honoraria and medical directorship fees from Fresenius and DaVita. Dr. Davison has reported no relevant financial relationships.

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

According to the Centers for Disease Control and Prevention (CDC), approximately 795,000 strokes occur in the United States yearly and are the fifth leading cause of death.¹ The CDC also states that about 43 million Americans who could benefit from cholesterol medication are currently taking them.² As of 2019, West Virginia, Ohio, and Kentucky are 3 states with the highest rates of heart disease mortality.³

Low-density lipoprotein cholesterol (LDL-C) accumulates on the walls of blood vessels, which can lead to coronary heart disease. However, some LDL-C is necessary to maintain proper brain function. Guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) recommend LDL-C goal levels < 70 mg/dL.⁴ Yet, there is no consensus on how low LDL-C levels should be. According to clinical practice guidelines for dyslipidemia, developed by the US Department of Veterans Affairs (VA) and US Department of Defense, statin medications are first-line agents for lowering LDL-C. The intensity of the statin medication is based on primary or secondary prevention, atherosclerotic cardiovascular disease (ASCVD) risk, and current LDL-C levels prior to treatment.⁵

Statin medications are used for primary and secondary prevention of ASCVD. In addition, statin medications decrease total cholesterol, LDL-C, and triglycerides while causing a mild increase in high-density lipoprotein cholesterol. Although statin medications are first-line therapy for LDL-C lowering, other medications can be used to assist in decreasing LDL-C. Ezetimibe, fenofibrates, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can also be used.⁵ Statin medications do pose a risk of severe adverse drug reactions (ADRs), such as rhabdomyolysis and myopathy.⁶

One prospective cohort study looked at 27,937 women and analyzed total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, and strokes. The study noted a mean 19.3-year follow-up and within that follow-up, 137 hemorrhagic strokes occurred. Based on the study’s results, LDL-C levels < 70 mg/dL had 2.17 times the risk of experiencing a hemorrhagic stroke.⁷ A meta-analysis of prospective studies analyzed 476,173 patients and 7487 hemorrhagic stroke cases. This review concluded that a 10 mg/dL increase in LDL-C was associated with a 3% lower risk of hemorrhagic stroke.⁸

An observational study conducted in Asia of Chinese adults found that 22% of all strokes were hemorrhagic. The incidence of the hemorrhagic strokes was higher for patients who had an LDL-C < 1.8 mmol/L than those who had an LDL-C between 1.8 and 2.6 mmol/L. This study also showed that if hypertension was inadequately treated, the risk of hemorrhagic stroke increased. This study concluded that the benefit of reducing ASCVD outweighs the small risk of hemorrhagic strokes.⁹

Another prospective cohort study included 96,043 stroke-free participants and analyzed LDL-C concentrations and incidence of intracranial hemorrhage. The average LDL-C concentrations were calculated from data collected in 4 separate reporting years, and incidence of intracranial hemorrhage was confirmed through review of medication records. Over a 9-year follow-up period, the study concluded that participants with an LDL-C level of < 70 mg/dL had a significantly higher risk of developing intracranial hemorrhage than participants with LDL-C levels 70 to 99 mg/dL.¹⁰

The safety and effects of prolonged very low LDL-C levels are currently unknown. The current study sought to gather information to determine the risks of very low LDL-C levels in a veteran population.

Methods

A retrospective chart review was conducted on patients aged 18 to 90 years receiving care at the Hershel “Woody” Williams Veterans Affairs Medical Center (HWW VAMC) in Huntington, West Virginia, between January 1, 2010, and September 1, 2020. Approval of the current study was obtained through the Marshall University Institutional Review Board, HWW VAMC Research and Development Committee, and Veterans Health Administration (VHA) DATA Access Request Tracker (DART)/VA Informatic and Computing Infrastructure (VINCI). Data were obtained via the VHA Corporate Data Warehouse (CDW) for the HWW VAMC using Microsoft Structured Query Language (SQL) server available in VINCI. Analysis of the data was conducted using STATA v. 15.

Patients were included if they had a diagnosis of hyperlipidemia/dyslipidemia, received treatment with HMG-CoA reductase inhibitors or PCSK9 medications, and had an LDL-C level ≤ 40 mg/dL. The primary outcome was the rate of intracranial hemorrhage that could be caused by very low LDL-C levels. The secondary outcomes included actions taken by clinicians to address LDL-C level < 40 mg/dL, ADRs, duration of therapy, and medication adherence. Patients were excluded if they were aged < 18 or > 90 years, were pregnant during the study period, had hypothyroidism, received chronic anticoagulation medications, or had a triglyceride level > 300 mg/dL.

Results

The study included 3027 patients. Of those patients, 78 patients were female while 2949 were male, and the mean (SD) age was 68.3 (9.4) years. A subsample of 32 patients was analyzed to determine whether an ADR was noted or low LDL-C level was addressed in the chart. The subsample size was determined through chart review and included patients who had a documented intracranial hemorrhage. None of the 32 patients had an ADR documented, and 6 (19%) had the low LDL-C level addressed in the chart by monitoring levels, reducing statin doses, or discontinuing the medication. Of the total population analyzed, 8 patients (0.3%) had a documented intracranial hemorrhage within 1 year following the low LDL-C level.

We also analyzed the intensity of statin related to the low LDL-C level (Table 1).

Eight patients of the total sample analyzed had an intracranial hemorrhage within 1 year of having a recorded LDL-C level < 40 mg/dL. Secondarily, 32 patients had clinicians address an LDL-C level < 40 mg/dL through documentation or modifying the medication therapy. The most common ADRs among all medications analyzed were leg and joint pain, rash, and cramps. Of all medications included in this study, the mean duration of therapy was > 1 year, which would allow them to affect LDL-C levels and have those levels monitored and recorded in patients’ charts.

Discussion

When comparing our primary outcome of risk of intracranial hemorrhage with previous literature, the results are consistent with previous outcomes. Previous literature had a smaller sample size but analyzed LDL-C levels < 50 mg/dL and had an outcome of 48 patients experiencing an intracranial hemorrhage within 1 year of an LDL-C level < 50 mg/dL. Due to this study having stricter parameters of LDL-C levels < 40 mg/dL, there were fewer patients with documented intracranial hemorrhages. With there being a risk of intracranial hemorrhage with low LDL-C levels, the results demonstrate the need to monitor and address LDL-C levels.

Limitations

There were several notable limitations to this study. The retrospective, single-center nature coupled with the predominately male study population may affect the generalizability of the study results to patients outside of the facility in which the study was performed. Additionally, the study only included statin medications and PCSK9 inhibitors. With future studies, all lipid-lowering medications could be analyzed. The study was largely reliant on the proper documentation of International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes exclusive to the HWW VAMC, which may exclude patients who first present to outside facilities. Due to time restraints, the incidence of hemorrhage was only analyzed 1 year following an LDL-C level < 40 mg/dL. For considerations for future investigation, the length of time to analyze incidence of hemorrhage could be expanded to be similar to previous studies, and the study could be expanded across the local Veterans Integrated Service Network or VA system. Additionally, the study could have analyzed the percentage of time a patient had an LDL-C level < 40 mg/dL in their lifetime.

Conclusions

These results show there is a risk that patients with an LDL-C level < 40 mg/dL may experience an intracranial hemorrhage. As seen by the results, there is a clinical need for practitioners to routinely monitor and address LDL-C levels. With various guidelines that recommend starting statin medication to reduce risk of ASCVD, it is necessary that practitioners routinely monitor cholesterol levels and adjust the medications according to laboratory results.¹¹

Within 1 year of an LDL-C level < 40 mg/dL, 0.3% of patients had an intracranial hemorrhage. There was no statistical significance between the rate of ADRs among the medications analyzed. High-intensity statin medications were statistically significant in resulting in an LDL-C level < 40 mg/dL compared with moderate- and low-intensity statin medications. Of the 32 subsample of patients, LDL-C levels < 40 mg/mL are not routinely being addressed in the chart by the clinician.

According to the Centers for Disease Control and Prevention (CDC), approximately 795,000 strokes occur in the United States yearly and are the fifth leading cause of death.¹ The CDC also states that about 43 million Americans who could benefit from cholesterol medication are currently taking them.² As of 2019, West Virginia, Ohio, and Kentucky are 3 states with the highest rates of heart disease mortality.³

Low-density lipoprotein cholesterol (LDL-C) accumulates on the walls of blood vessels, which can lead to coronary heart disease. However, some LDL-C is necessary to maintain proper brain function. Guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) recommend LDL-C goal levels < 70 mg/dL.⁴ Yet, there is no consensus on how low LDL-C levels should be. According to clinical practice guidelines for dyslipidemia, developed by the US Department of Veterans Affairs (VA) and US Department of Defense, statin medications are first-line agents for lowering LDL-C. The intensity of the statin medication is based on primary or secondary prevention, atherosclerotic cardiovascular disease (ASCVD) risk, and current LDL-C levels prior to treatment.⁵

Statin medications are used for primary and secondary prevention of ASCVD. In addition, statin medications decrease total cholesterol, LDL-C, and triglycerides while causing a mild increase in high-density lipoprotein cholesterol. Although statin medications are first-line therapy for LDL-C lowering, other medications can be used to assist in decreasing LDL-C. Ezetimibe, fenofibrates, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can also be used.⁵ Statin medications do pose a risk of severe adverse drug reactions (ADRs), such as rhabdomyolysis and myopathy.⁶

One prospective cohort study looked at 27,937 women and analyzed total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, and strokes. The study noted a mean 19.3-year follow-up and within that follow-up, 137 hemorrhagic strokes occurred. Based on the study’s results, LDL-C levels < 70 mg/dL had 2.17 times the risk of experiencing a hemorrhagic stroke.⁷ A meta-analysis of prospective studies analyzed 476,173 patients and 7487 hemorrhagic stroke cases. This review concluded that a 10 mg/dL increase in LDL-C was associated with a 3% lower risk of hemorrhagic stroke.⁸

An observational study conducted in Asia of Chinese adults found that 22% of all strokes were hemorrhagic. The incidence of the hemorrhagic strokes was higher for patients who had an LDL-C < 1.8 mmol/L than those who had an LDL-C between 1.8 and 2.6 mmol/L. This study also showed that if hypertension was inadequately treated, the risk of hemorrhagic stroke increased. This study concluded that the benefit of reducing ASCVD outweighs the small risk of hemorrhagic strokes.⁹

Another prospective cohort study included 96,043 stroke-free participants and analyzed LDL-C concentrations and incidence of intracranial hemorrhage. The average LDL-C concentrations were calculated from data collected in 4 separate reporting years, and incidence of intracranial hemorrhage was confirmed through review of medication records. Over a 9-year follow-up period, the study concluded that participants with an LDL-C level of < 70 mg/dL had a significantly higher risk of developing intracranial hemorrhage than participants with LDL-C levels 70 to 99 mg/dL.¹⁰

The safety and effects of prolonged very low LDL-C levels are currently unknown. The current study sought to gather information to determine the risks of very low LDL-C levels in a veteran population.

Methods

A retrospective chart review was conducted on patients aged 18 to 90 years receiving care at the Hershel “Woody” Williams Veterans Affairs Medical Center (HWW VAMC) in Huntington, West Virginia, between January 1, 2010, and September 1, 2020. Approval of the current study was obtained through the Marshall University Institutional Review Board, HWW VAMC Research and Development Committee, and Veterans Health Administration (VHA) DATA Access Request Tracker (DART)/VA Informatic and Computing Infrastructure (VINCI). Data were obtained via the VHA Corporate Data Warehouse (CDW) for the HWW VAMC using Microsoft Structured Query Language (SQL) server available in VINCI. Analysis of the data was conducted using STATA v. 15.

Patients were included if they had a diagnosis of hyperlipidemia/dyslipidemia, received treatment with HMG-CoA reductase inhibitors or PCSK9 medications, and had an LDL-C level ≤ 40 mg/dL. The primary outcome was the rate of intracranial hemorrhage that could be caused by very low LDL-C levels. The secondary outcomes included actions taken by clinicians to address LDL-C level < 40 mg/dL, ADRs, duration of therapy, and medication adherence. Patients were excluded if they were aged < 18 or > 90 years, were pregnant during the study period, had hypothyroidism, received chronic anticoagulation medications, or had a triglyceride level > 300 mg/dL.

Results

The study included 3027 patients. Of those patients, 78 patients were female while 2949 were male, and the mean (SD) age was 68.3 (9.4) years. A subsample of 32 patients was analyzed to determine whether an ADR was noted or low LDL-C level was addressed in the chart. The subsample size was determined through chart review and included patients who had a documented intracranial hemorrhage. None of the 32 patients had an ADR documented, and 6 (19%) had the low LDL-C level addressed in the chart by monitoring levels, reducing statin doses, or discontinuing the medication. Of the total population analyzed, 8 patients (0.3%) had a documented intracranial hemorrhage within 1 year following the low LDL-C level.

We also analyzed the intensity of statin related to the low LDL-C level (Table 1).

Eight patients of the total sample analyzed had an intracranial hemorrhage within 1 year of having a recorded LDL-C level < 40 mg/dL. Secondarily, 32 patients had clinicians address an LDL-C level < 40 mg/dL through documentation or modifying the medication therapy. The most common ADRs among all medications analyzed were leg and joint pain, rash, and cramps. Of all medications included in this study, the mean duration of therapy was > 1 year, which would allow them to affect LDL-C levels and have those levels monitored and recorded in patients’ charts.

Discussion

When comparing our primary outcome of risk of intracranial hemorrhage with previous literature, the results are consistent with previous outcomes. Previous literature had a smaller sample size but analyzed LDL-C levels < 50 mg/dL and had an outcome of 48 patients experiencing an intracranial hemorrhage within 1 year of an LDL-C level < 50 mg/dL. Due to this study having stricter parameters of LDL-C levels < 40 mg/dL, there were fewer patients with documented intracranial hemorrhages. With there being a risk of intracranial hemorrhage with low LDL-C levels, the results demonstrate the need to monitor and address LDL-C levels.

Limitations

There were several notable limitations to this study. The retrospective, single-center nature coupled with the predominately male study population may affect the generalizability of the study results to patients outside of the facility in which the study was performed. Additionally, the study only included statin medications and PCSK9 inhibitors. With future studies, all lipid-lowering medications could be analyzed. The study was largely reliant on the proper documentation of International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes exclusive to the HWW VAMC, which may exclude patients who first present to outside facilities. Due to time restraints, the incidence of hemorrhage was only analyzed 1 year following an LDL-C level < 40 mg/dL. For considerations for future investigation, the length of time to analyze incidence of hemorrhage could be expanded to be similar to previous studies, and the study could be expanded across the local Veterans Integrated Service Network or VA system. Additionally, the study could have analyzed the percentage of time a patient had an LDL-C level < 40 mg/dL in their lifetime.

Conclusions

These results show there is a risk that patients with an LDL-C level < 40 mg/dL may experience an intracranial hemorrhage. As seen by the results, there is a clinical need for practitioners to routinely monitor and address LDL-C levels. With various guidelines that recommend starting statin medication to reduce risk of ASCVD, it is necessary that practitioners routinely monitor cholesterol levels and adjust the medications according to laboratory results.¹¹

Within 1 year of an LDL-C level < 40 mg/dL, 0.3% of patients had an intracranial hemorrhage. There was no statistical significance between the rate of ADRs among the medications analyzed. High-intensity statin medications were statistically significant in resulting in an LDL-C level < 40 mg/dL compared with moderate- and low-intensity statin medications. Of the 32 subsample of patients, LDL-C levels < 40 mg/mL are not routinely being addressed in the chart by the clinician.

According to the Centers for Disease Control and Prevention (CDC), approximately 795,000 strokes occur in the United States yearly and are the fifth leading cause of death.¹ The CDC also states that about 43 million Americans who could benefit from cholesterol medication are currently taking them.² As of 2019, West Virginia, Ohio, and Kentucky are 3 states with the highest rates of heart disease mortality.³

Low-density lipoprotein cholesterol (LDL-C) accumulates on the walls of blood vessels, which can lead to coronary heart disease. However, some LDL-C is necessary to maintain proper brain function. Guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) recommend LDL-C goal levels < 70 mg/dL.⁴ Yet, there is no consensus on how low LDL-C levels should be. According to clinical practice guidelines for dyslipidemia, developed by the US Department of Veterans Affairs (VA) and US Department of Defense, statin medications are first-line agents for lowering LDL-C. The intensity of the statin medication is based on primary or secondary prevention, atherosclerotic cardiovascular disease (ASCVD) risk, and current LDL-C levels prior to treatment.⁵

Statin medications are used for primary and secondary prevention of ASCVD. In addition, statin medications decrease total cholesterol, LDL-C, and triglycerides while causing a mild increase in high-density lipoprotein cholesterol. Although statin medications are first-line therapy for LDL-C lowering, other medications can be used to assist in decreasing LDL-C. Ezetimibe, fenofibrates, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can also be used.⁵ Statin medications do pose a risk of severe adverse drug reactions (ADRs), such as rhabdomyolysis and myopathy.⁶

One prospective cohort study looked at 27,937 women and analyzed total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, and strokes. The study noted a mean 19.3-year follow-up and within that follow-up, 137 hemorrhagic strokes occurred. Based on the study’s results, LDL-C levels < 70 mg/dL had 2.17 times the risk of experiencing a hemorrhagic stroke.⁷ A meta-analysis of prospective studies analyzed 476,173 patients and 7487 hemorrhagic stroke cases. This review concluded that a 10 mg/dL increase in LDL-C was associated with a 3% lower risk of hemorrhagic stroke.⁸

An observational study conducted in Asia of Chinese adults found that 22% of all strokes were hemorrhagic. The incidence of the hemorrhagic strokes was higher for patients who had an LDL-C < 1.8 mmol/L than those who had an LDL-C between 1.8 and 2.6 mmol/L. This study also showed that if hypertension was inadequately treated, the risk of hemorrhagic stroke increased. This study concluded that the benefit of reducing ASCVD outweighs the small risk of hemorrhagic strokes.⁹

Another prospective cohort study included 96,043 stroke-free participants and analyzed LDL-C concentrations and incidence of intracranial hemorrhage. The average LDL-C concentrations were calculated from data collected in 4 separate reporting years, and incidence of intracranial hemorrhage was confirmed through review of medication records. Over a 9-year follow-up period, the study concluded that participants with an LDL-C level of < 70 mg/dL had a significantly higher risk of developing intracranial hemorrhage than participants with LDL-C levels 70 to 99 mg/dL.¹⁰

The safety and effects of prolonged very low LDL-C levels are currently unknown. The current study sought to gather information to determine the risks of very low LDL-C levels in a veteran population.

Methods

A retrospective chart review was conducted on patients aged 18 to 90 years receiving care at the Hershel “Woody” Williams Veterans Affairs Medical Center (HWW VAMC) in Huntington, West Virginia, between January 1, 2010, and September 1, 2020. Approval of the current study was obtained through the Marshall University Institutional Review Board, HWW VAMC Research and Development Committee, and Veterans Health Administration (VHA) DATA Access Request Tracker (DART)/VA Informatic and Computing Infrastructure (VINCI). Data were obtained via the VHA Corporate Data Warehouse (CDW) for the HWW VAMC using Microsoft Structured Query Language (SQL) server available in VINCI. Analysis of the data was conducted using STATA v. 15.

Patients were included if they had a diagnosis of hyperlipidemia/dyslipidemia, received treatment with HMG-CoA reductase inhibitors or PCSK9 medications, and had an LDL-C level ≤ 40 mg/dL. The primary outcome was the rate of intracranial hemorrhage that could be caused by very low LDL-C levels. The secondary outcomes included actions taken by clinicians to address LDL-C level < 40 mg/dL, ADRs, duration of therapy, and medication adherence. Patients were excluded if they were aged < 18 or > 90 years, were pregnant during the study period, had hypothyroidism, received chronic anticoagulation medications, or had a triglyceride level > 300 mg/dL.

Results

The study included 3027 patients. Of those patients, 78 patients were female while 2949 were male, and the mean (SD) age was 68.3 (9.4) years. A subsample of 32 patients was analyzed to determine whether an ADR was noted or low LDL-C level was addressed in the chart. The subsample size was determined through chart review and included patients who had a documented intracranial hemorrhage. None of the 32 patients had an ADR documented, and 6 (19%) had the low LDL-C level addressed in the chart by monitoring levels, reducing statin doses, or discontinuing the medication. Of the total population analyzed, 8 patients (0.3%) had a documented intracranial hemorrhage within 1 year following the low LDL-C level.

We also analyzed the intensity of statin related to the low LDL-C level (Table 1).

Eight patients of the total sample analyzed had an intracranial hemorrhage within 1 year of having a recorded LDL-C level < 40 mg/dL. Secondarily, 32 patients had clinicians address an LDL-C level < 40 mg/dL through documentation or modifying the medication therapy. The most common ADRs among all medications analyzed were leg and joint pain, rash, and cramps. Of all medications included in this study, the mean duration of therapy was > 1 year, which would allow them to affect LDL-C levels and have those levels monitored and recorded in patients’ charts.

Discussion

When comparing our primary outcome of risk of intracranial hemorrhage with previous literature, the results are consistent with previous outcomes. Previous literature had a smaller sample size but analyzed LDL-C levels < 50 mg/dL and had an outcome of 48 patients experiencing an intracranial hemorrhage within 1 year of an LDL-C level < 50 mg/dL. Due to this study having stricter parameters of LDL-C levels < 40 mg/dL, there were fewer patients with documented intracranial hemorrhages. With there being a risk of intracranial hemorrhage with low LDL-C levels, the results demonstrate the need to monitor and address LDL-C levels.

Limitations

There were several notable limitations to this study. The retrospective, single-center nature coupled with the predominately male study population may affect the generalizability of the study results to patients outside of the facility in which the study was performed. Additionally, the study only included statin medications and PCSK9 inhibitors. With future studies, all lipid-lowering medications could be analyzed. The study was largely reliant on the proper documentation of International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes exclusive to the HWW VAMC, which may exclude patients who first present to outside facilities. Due to time restraints, the incidence of hemorrhage was only analyzed 1 year following an LDL-C level < 40 mg/dL. For considerations for future investigation, the length of time to analyze incidence of hemorrhage could be expanded to be similar to previous studies, and the study could be expanded across the local Veterans Integrated Service Network or VA system. Additionally, the study could have analyzed the percentage of time a patient had an LDL-C level < 40 mg/dL in their lifetime.

Conclusions

These results show there is a risk that patients with an LDL-C level < 40 mg/dL may experience an intracranial hemorrhage. As seen by the results, there is a clinical need for practitioners to routinely monitor and address LDL-C levels. With various guidelines that recommend starting statin medication to reduce risk of ASCVD, it is necessary that practitioners routinely monitor cholesterol levels and adjust the medications according to laboratory results.¹¹

Within 1 year of an LDL-C level < 40 mg/dL, 0.3% of patients had an intracranial hemorrhage. There was no statistical significance between the rate of ADRs among the medications analyzed. High-intensity statin medications were statistically significant in resulting in an LDL-C level < 40 mg/dL compared with moderate- and low-intensity statin medications. Of the 32 subsample of patients, LDL-C levels < 40 mg/mL are not routinely being addressed in the chart by the clinician.

The use of low-dose aspirin for the primary prevention of cardiovascular disease (CVD) morbidity and mortality continues to be controversial, particularly for older adults. Recently published, robust randomized controlled trials have revealed less cardiovascular benefit from aspirin for primary prevention compared with previous trials; additionally, an increased risk of major bleeding events has been notably more prevalent in older adults.^1-5 These trials have suggested that preventative aspirin use in older adults confers less benefit than other therapies for decreasing atherosclerotic CVD (ASCVD) risk, including blood pressure (BP) control, cholesterol management, and tobacco cessation.^1,6

A recent meta-analysis indicated a composite cardiovascular risk reduction in patients aged 53 to 74 years taking aspirin vs no aspirin; however, this benefit was offset with an even greater increased risk of major bleeding.⁷ This trend was consistent regardless of stratification by 10-year ASCVD risk or presence of diabetes mellitus (DM) diagnosis.^7,8 Additionally, the recently published Aspirin in Reducing Events in the Elderly (ASPREE) trial studied the impacts of aspirin use in healthy adults aged ≥ 70 years and aged ≥ 65 years among Black and Hispanic adults.⁴ The study concluded that the risk of major bleeding with aspirin use was even higher vs the potential cardiovascular benefit in older adults.⁴

With this emerging evidence, guidelines have been updated to represent the need for risk vs benefit considerations regarding aspirin use for primary prevention in older adults.^1,9,10 The most recent guideline update from the American College of Cardiology and American Heart Association (ACC/AHA) recommends against the routine use of aspirin in patients aged > 70 years or those with bleeding risk factors.¹ The guideline recommends considering aspirin use for patients ages 40 to 70 years only after a patient-specific risk vs benefit discussion.¹ Furthermore, the 2020 American Diabetes Association guideline recommends considering aspirin use for primary prevention in adults with DM between ages 50 and 70 only after a risk vs benefit discussion of patient-specific bleeding risk factors and ASCVD risk-enhancing factors.¹⁰

Despite the demonstrated risks for bleeding with the routine use of aspirin, studies indicate that aspirin continues to be used commonly among older adults, often when unnecessary. In the 2017 National Health Interview Survey, about 23% of adults aged > 40 years in the United States without CVD used aspirin daily, and 23% of these did so without recommendation from a health care professional.¹¹ Furthermore, nearly half of adults ages ≥ 70 years and nearly one-quarter of adults with a history of peptic ulcer disease used aspirin daily.¹¹ Although the most recent guidelines from the ACC/AHA do not recommend a 10-year ASCVD risk threshold for therapy, one study illustrated that 12% of older adult patients were inappropriately prescribed aspirin for primary prevention despite a 10-year ASCVD risk of < 6%.^1,12 These studies highlight the large proportion of individuals, particularly older adults, who may be inappropriately taking aspirin for primary prevention.

Deprescribing Program

Deprescribing potentially inappropriate medications (PIMs) is particularly important in the older adult population, as these individuals experience a high risk of adverse effects (AEs), polypharmacy, cognitive decline, and falls related to medication use.^6,13-17 Evidence suggests that mortality outcomes are improved with the implementation of targeted deprescribing efforts based on patient-specific factors.¹⁸ Additionally, deprescribing unnecessary medications may improve adherence to other essential medications and reduce financial burdens.¹⁹ Pharmacists play a crucial role among health care professionals in the implementation of deprescribing practices, and studies have shown that physicians are highly accepting of pharmacists’ deprescribing recommendations.^13,20-22

Despite the evidence for the benefits of deprescribing, limited data are available regarding the impact and feasibility of a targeted aspirin deprescribing approach by nonphysician practitioners.²³ The objective of this study was to implement and evaluate the success of a pharmacist-driven aspirin deprescribing protocol for older adults in a primary care setting.

This aspirin deprescribing protocol was developed by ambulatory care clinical pharmacist or clinical pharmacist practitioners (CPPs), at the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. Within the US Department of Veterans Affairs (VA) health care system, CPPs work under a broad scope of practice with the ability to independently prescribe and monitor medications. The protocol was reviewed by physician stakeholders in both primary care and cardiology and a list was generated, including patients from 2 primary care panels aged ≥ 70 years with aspirin on their medication list, either as a prescription or over-the-counter medication, using the VA Information System Technology and Architecture. A CPP or supervised pharmacy intern identified patients from this list who were appropriate for risk/benefit discussions regarding the discontinuation of aspirin. Patients were excluded from the intervention if they had a history of clinical ASCVD, including myocardial infarction (MI), stable or unstable angina, coronary artery disease (CAD), coronary or other arterial revascularization, cerebrovascular accident (CVA), transient ischemic accident (TIA), or peripheral artery disease (PAD), or another documented indication for aspirin use, including pain, flushing (with niacin use), venous thromboembolism prophylaxis, valvular heart disease, or acute or recurrent pericarditis.

After identifying eligible patients, a CPP or pharmacy intern contacted patients by telephone, following a script to guide conversation. All patients were screened for potential appropriate aspirin indications, particularly any history of MI, CAD, CVA, TIA, PAD, or other clinical ASCVD. The patient was asked about their rationale for taking aspirin and patient-specific ASCVD risk-enhancing factors and bleeding risk factors and educated them on lifestyle modalities to reduce ASCVD risk, using the script as a guide. ASCVD risk-enhancing factors included family history of premature MI, inability to achieve BP goal, DM with the inability to achieve blood glucose or hemoglobin A_1c goal, tobacco use, or inadequate statin therapy. Bleeding risk factors included a history of gastrointestinal bleed or peptic ulcer disease, concurrent use of medications that increase bleeding risk, chronic kidney disease, or thrombocytopenia.

Through shared decision making with careful consideration of these factors, we reached a conclusion with each patient to either continue or to deprescribe aspirin. Each discussion was documented in the electronic health record (EHR) using a standard documentation template (eAppendix, available at doi:10.12788/fp.0320). The patient’s medication list also was updated to reflect changes in aspirin use. For patients who declined deprescribing, the CPP or pharmacy intern asked the patient for their primary reason for preferring to continue aspirin, which was subsequently categorized as one of the following: no prior concerns with bleeding, concerns about a future cardiovascular event, wishing to discuss further with their primary care practitioner (PCP), or identifying an appropriate use for aspirin not evident through record review. For the patients who wished to further discuss the issue with their PCP before deprescribing, the patient’s PCP was notified of this preference by a record alert to the note documenting the encounter, and the patient was also encouraged to follow up about this issue. A voicemail was left if the patient did not answer requesting a call back, and a second attempt was made within 2 weeks.

Data Collected

We collected data to assess the proportion of patients for whom aspirin for primary prevention was discontinued. For patients who declined deprescribing, we documented the rationale for continuing aspirin. Additionally, the feasibility of implementation was assessed, including pharmacist time spent on each record review and intervention. Descriptive statistics were generated to evaluate baseline characteristics and intervention outcomes. The time to completion of these tasks was summarized with descriptive statistics.

We reviewed 459 patient records, and 110 were determined eligible for risk/benefit discussions.

Results of the time-study analysis for each intervention indicated that a pharmacy intern or pharmacist spent about 2 minutes reviewing the record of each patient to determine eligibility for risk/benefit discussions. The 110 patients identified as eligible were 24% of the 459 records reviewed. An average (range) of 12 (6-20) minutes was spent on the telephone call plus documentation for each patient contacted. Additionally, we estimated that CPPs and pharmacy interns spent an approximate combined 12 hours in the development and review of materials for this program, including the protocol, script, and documentation templates. This also included about 1 hour to identify appropriate parameters for, and generate, the eligible patient list.

Discussion

The implementation of a pharmacist-driven aspirin deprescribing protocol for older adults in a primary care setting led to the discontinuation of inappropriate aspirin use in nearly half of older adults contacted. Furthermore, opportunities were identified to update medication lists to reflect previously self-discontinued aspirin for older adults. Just over one-quarter of those contacted declined to discontinue or reduce their aspirin dose. It is hypothesized that with these targeted deprescribing interventions, overall risk reduction for bleeding and polypharmacy will be observed for older adults.¹

In addition to deprescribing aspirin, CPPs used shared decision making to initiate risk/benefit discussions and to educate on targeted lifestyle modifications to lower ASCVD risk. While not all patients agreed to discontinue aspirin, all were provided education that may empower them to engage in future discussions with PCPs regarding appropriate aspirin use. Previous pharmacist-led deprescribing initiatives for proton pump inhibitors and other PIMs have indicated that a large percentage of patients who opt to further discuss a deprescribing concern with their PCPs ultimately resulted in deprescribing outcomes.^24,25 Additionally, a recent trial examining pharmacist-led deprescribing of 4 common PIMs in older adults compared the impact of pharmacists leading educational interventions directly to patients with pharmacists making deprescribing recommendations to physicians. Deprescribing was more successful when patients were involved in the decision-making process.²⁶

Limitations

Although this quality improvement initiative resulted in the deprescribing of inappropriate aspirin for many older adults, a limitation is the small sample size within a single institution. The population of male veterans also may limit generalizability to nonmale and nonveteran older adults. As the protocol was initiated within a limited number of primary care teams initially, future implementation into additional primary care teams will increase the number of older adults impacted by risk/benefit discussions regarding aspirin use. This work may not be generalizable to other health care systems. Many patients within the VA receive both their primary and specialty care within the system, which facilitates communication and collaboration between primary and specialty practitioners. The protocol may require workflow adjustments for patients receiving care within multiple systems. Additionally, although the deprescribing protocol was created in collaboration with physicians, CPPs within the VA work under a broad scope of practice that includes independent medication prescribing, deprescribing, and monitoring. This may be a consideration when implementing similar protocols at other sites, as collaborative practice agreements may need to be in place.

Future Directions

The time required to complete these interventions was generally feasible, though this intervention would require some workflow alteration to be incorporated routinely into a CPP’s schedule. The telephone calls were completed as isolated interventions and were not incorporated into existing scheduled primary care appointments. In the future, the aspirin deprescribing protocol could be incorporated into existing pharmacist-led primary care appointments. Based on the outcomes of this study, CPPs are leading an initiative to develop an aspirin deprescribing clinical reminder tool, which may be quickly inserted into a progress note within the EHR and may be incorporated into any primary care visit led by a CPP or PCP.

Conclusions

This study demonstrates that a pharmacist-led aspirin deprescribing protocol in the ambulatory care pharmacy setting was successful in the discontinuation of unnecessary aspirin use in older adults. The protocol also provided opportunities for education on ASCVD risk reduction in all older adults reached. These findings highlight the role of pharmacists in deprescribing PIMs for older adults and identifying opportunities to further streamline risk/benefit discussions on aspirin deprescribing potential within primary care visits.

The use of low-dose aspirin for the primary prevention of cardiovascular disease (CVD) morbidity and mortality continues to be controversial, particularly for older adults. Recently published, robust randomized controlled trials have revealed less cardiovascular benefit from aspirin for primary prevention compared with previous trials; additionally, an increased risk of major bleeding events has been notably more prevalent in older adults.^1-5 These trials have suggested that preventative aspirin use in older adults confers less benefit than other therapies for decreasing atherosclerotic CVD (ASCVD) risk, including blood pressure (BP) control, cholesterol management, and tobacco cessation.^1,6

A recent meta-analysis indicated a composite cardiovascular risk reduction in patients aged 53 to 74 years taking aspirin vs no aspirin; however, this benefit was offset with an even greater increased risk of major bleeding.⁷ This trend was consistent regardless of stratification by 10-year ASCVD risk or presence of diabetes mellitus (DM) diagnosis.^7,8 Additionally, the recently published Aspirin in Reducing Events in the Elderly (ASPREE) trial studied the impacts of aspirin use in healthy adults aged ≥ 70 years and aged ≥ 65 years among Black and Hispanic adults.⁴ The study concluded that the risk of major bleeding with aspirin use was even higher vs the potential cardiovascular benefit in older adults.⁴

With this emerging evidence, guidelines have been updated to represent the need for risk vs benefit considerations regarding aspirin use for primary prevention in older adults.^1,9,10 The most recent guideline update from the American College of Cardiology and American Heart Association (ACC/AHA) recommends against the routine use of aspirin in patients aged > 70 years or those with bleeding risk factors.¹ The guideline recommends considering aspirin use for patients ages 40 to 70 years only after a patient-specific risk vs benefit discussion.¹ Furthermore, the 2020 American Diabetes Association guideline recommends considering aspirin use for primary prevention in adults with DM between ages 50 and 70 only after a risk vs benefit discussion of patient-specific bleeding risk factors and ASCVD risk-enhancing factors.¹⁰

Despite the demonstrated risks for bleeding with the routine use of aspirin, studies indicate that aspirin continues to be used commonly among older adults, often when unnecessary. In the 2017 National Health Interview Survey, about 23% of adults aged > 40 years in the United States without CVD used aspirin daily, and 23% of these did so without recommendation from a health care professional.¹¹ Furthermore, nearly half of adults ages ≥ 70 years and nearly one-quarter of adults with a history of peptic ulcer disease used aspirin daily.¹¹ Although the most recent guidelines from the ACC/AHA do not recommend a 10-year ASCVD risk threshold for therapy, one study illustrated that 12% of older adult patients were inappropriately prescribed aspirin for primary prevention despite a 10-year ASCVD risk of < 6%.^1,12 These studies highlight the large proportion of individuals, particularly older adults, who may be inappropriately taking aspirin for primary prevention.

Deprescribing Program

Deprescribing potentially inappropriate medications (PIMs) is particularly important in the older adult population, as these individuals experience a high risk of adverse effects (AEs), polypharmacy, cognitive decline, and falls related to medication use.^6,13-17 Evidence suggests that mortality outcomes are improved with the implementation of targeted deprescribing efforts based on patient-specific factors.¹⁸ Additionally, deprescribing unnecessary medications may improve adherence to other essential medications and reduce financial burdens.¹⁹ Pharmacists play a crucial role among health care professionals in the implementation of deprescribing practices, and studies have shown that physicians are highly accepting of pharmacists’ deprescribing recommendations.^13,20-22

Despite the evidence for the benefits of deprescribing, limited data are available regarding the impact and feasibility of a targeted aspirin deprescribing approach by nonphysician practitioners.²³ The objective of this study was to implement and evaluate the success of a pharmacist-driven aspirin deprescribing protocol for older adults in a primary care setting.

This aspirin deprescribing protocol was developed by ambulatory care clinical pharmacist or clinical pharmacist practitioners (CPPs), at the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. Within the US Department of Veterans Affairs (VA) health care system, CPPs work under a broad scope of practice with the ability to independently prescribe and monitor medications. The protocol was reviewed by physician stakeholders in both primary care and cardiology and a list was generated, including patients from 2 primary care panels aged ≥ 70 years with aspirin on their medication list, either as a prescription or over-the-counter medication, using the VA Information System Technology and Architecture. A CPP or supervised pharmacy intern identified patients from this list who were appropriate for risk/benefit discussions regarding the discontinuation of aspirin. Patients were excluded from the intervention if they had a history of clinical ASCVD, including myocardial infarction (MI), stable or unstable angina, coronary artery disease (CAD), coronary or other arterial revascularization, cerebrovascular accident (CVA), transient ischemic accident (TIA), or peripheral artery disease (PAD), or another documented indication for aspirin use, including pain, flushing (with niacin use), venous thromboembolism prophylaxis, valvular heart disease, or acute or recurrent pericarditis.

After identifying eligible patients, a CPP or pharmacy intern contacted patients by telephone, following a script to guide conversation. All patients were screened for potential appropriate aspirin indications, particularly any history of MI, CAD, CVA, TIA, PAD, or other clinical ASCVD. The patient was asked about their rationale for taking aspirin and patient-specific ASCVD risk-enhancing factors and bleeding risk factors and educated them on lifestyle modalities to reduce ASCVD risk, using the script as a guide. ASCVD risk-enhancing factors included family history of premature MI, inability to achieve BP goal, DM with the inability to achieve blood glucose or hemoglobin A_1c goal, tobacco use, or inadequate statin therapy. Bleeding risk factors included a history of gastrointestinal bleed or peptic ulcer disease, concurrent use of medications that increase bleeding risk, chronic kidney disease, or thrombocytopenia.

Through shared decision making with careful consideration of these factors, we reached a conclusion with each patient to either continue or to deprescribe aspirin. Each discussion was documented in the electronic health record (EHR) using a standard documentation template (eAppendix, available at doi:10.12788/fp.0320). The patient’s medication list also was updated to reflect changes in aspirin use. For patients who declined deprescribing, the CPP or pharmacy intern asked the patient for their primary reason for preferring to continue aspirin, which was subsequently categorized as one of the following: no prior concerns with bleeding, concerns about a future cardiovascular event, wishing to discuss further with their primary care practitioner (PCP), or identifying an appropriate use for aspirin not evident through record review. For the patients who wished to further discuss the issue with their PCP before deprescribing, the patient’s PCP was notified of this preference by a record alert to the note documenting the encounter, and the patient was also encouraged to follow up about this issue. A voicemail was left if the patient did not answer requesting a call back, and a second attempt was made within 2 weeks.

Data Collected

We collected data to assess the proportion of patients for whom aspirin for primary prevention was discontinued. For patients who declined deprescribing, we documented the rationale for continuing aspirin. Additionally, the feasibility of implementation was assessed, including pharmacist time spent on each record review and intervention. Descriptive statistics were generated to evaluate baseline characteristics and intervention outcomes. The time to completion of these tasks was summarized with descriptive statistics.

We reviewed 459 patient records, and 110 were determined eligible for risk/benefit discussions.

Results of the time-study analysis for each intervention indicated that a pharmacy intern or pharmacist spent about 2 minutes reviewing the record of each patient to determine eligibility for risk/benefit discussions. The 110 patients identified as eligible were 24% of the 459 records reviewed. An average (range) of 12 (6-20) minutes was spent on the telephone call plus documentation for each patient contacted. Additionally, we estimated that CPPs and pharmacy interns spent an approximate combined 12 hours in the development and review of materials for this program, including the protocol, script, and documentation templates. This also included about 1 hour to identify appropriate parameters for, and generate, the eligible patient list.

Discussion

The implementation of a pharmacist-driven aspirin deprescribing protocol for older adults in a primary care setting led to the discontinuation of inappropriate aspirin use in nearly half of older adults contacted. Furthermore, opportunities were identified to update medication lists to reflect previously self-discontinued aspirin for older adults. Just over one-quarter of those contacted declined to discontinue or reduce their aspirin dose. It is hypothesized that with these targeted deprescribing interventions, overall risk reduction for bleeding and polypharmacy will be observed for older adults.¹

In addition to deprescribing aspirin, CPPs used shared decision making to initiate risk/benefit discussions and to educate on targeted lifestyle modifications to lower ASCVD risk. While not all patients agreed to discontinue aspirin, all were provided education that may empower them to engage in future discussions with PCPs regarding appropriate aspirin use. Previous pharmacist-led deprescribing initiatives for proton pump inhibitors and other PIMs have indicated that a large percentage of patients who opt to further discuss a deprescribing concern with their PCPs ultimately resulted in deprescribing outcomes.^24,25 Additionally, a recent trial examining pharmacist-led deprescribing of 4 common PIMs in older adults compared the impact of pharmacists leading educational interventions directly to patients with pharmacists making deprescribing recommendations to physicians. Deprescribing was more successful when patients were involved in the decision-making process.²⁶

Limitations

Although this quality improvement initiative resulted in the deprescribing of inappropriate aspirin for many older adults, a limitation is the small sample size within a single institution. The population of male veterans also may limit generalizability to nonmale and nonveteran older adults. As the protocol was initiated within a limited number of primary care teams initially, future implementation into additional primary care teams will increase the number of older adults impacted by risk/benefit discussions regarding aspirin use. This work may not be generalizable to other health care systems. Many patients within the VA receive both their primary and specialty care within the system, which facilitates communication and collaboration between primary and specialty practitioners. The protocol may require workflow adjustments for patients receiving care within multiple systems. Additionally, although the deprescribing protocol was created in collaboration with physicians, CPPs within the VA work under a broad scope of practice that includes independent medication prescribing, deprescribing, and monitoring. This may be a consideration when implementing similar protocols at other sites, as collaborative practice agreements may need to be in place.

Future Directions

The time required to complete these interventions was generally feasible, though this intervention would require some workflow alteration to be incorporated routinely into a CPP’s schedule. The telephone calls were completed as isolated interventions and were not incorporated into existing scheduled primary care appointments. In the future, the aspirin deprescribing protocol could be incorporated into existing pharmacist-led primary care appointments. Based on the outcomes of this study, CPPs are leading an initiative to develop an aspirin deprescribing clinical reminder tool, which may be quickly inserted into a progress note within the EHR and may be incorporated into any primary care visit led by a CPP or PCP.

Conclusions

This study demonstrates that a pharmacist-led aspirin deprescribing protocol in the ambulatory care pharmacy setting was successful in the discontinuation of unnecessary aspirin use in older adults. The protocol also provided opportunities for education on ASCVD risk reduction in all older adults reached. These findings highlight the role of pharmacists in deprescribing PIMs for older adults and identifying opportunities to further streamline risk/benefit discussions on aspirin deprescribing potential within primary care visits.

The use of low-dose aspirin for the primary prevention of cardiovascular disease (CVD) morbidity and mortality continues to be controversial, particularly for older adults. Recently published, robust randomized controlled trials have revealed less cardiovascular benefit from aspirin for primary prevention compared with previous trials; additionally, an increased risk of major bleeding events has been notably more prevalent in older adults.^1-5 These trials have suggested that preventative aspirin use in older adults confers less benefit than other therapies for decreasing atherosclerotic CVD (ASCVD) risk, including blood pressure (BP) control, cholesterol management, and tobacco cessation.^1,6

A recent meta-analysis indicated a composite cardiovascular risk reduction in patients aged 53 to 74 years taking aspirin vs no aspirin; however, this benefit was offset with an even greater increased risk of major bleeding.⁷ This trend was consistent regardless of stratification by 10-year ASCVD risk or presence of diabetes mellitus (DM) diagnosis.^7,8 Additionally, the recently published Aspirin in Reducing Events in the Elderly (ASPREE) trial studied the impacts of aspirin use in healthy adults aged ≥ 70 years and aged ≥ 65 years among Black and Hispanic adults.⁴ The study concluded that the risk of major bleeding with aspirin use was even higher vs the potential cardiovascular benefit in older adults.⁴

With this emerging evidence, guidelines have been updated to represent the need for risk vs benefit considerations regarding aspirin use for primary prevention in older adults.^1,9,10 The most recent guideline update from the American College of Cardiology and American Heart Association (ACC/AHA) recommends against the routine use of aspirin in patients aged > 70 years or those with bleeding risk factors.¹ The guideline recommends considering aspirin use for patients ages 40 to 70 years only after a patient-specific risk vs benefit discussion.¹ Furthermore, the 2020 American Diabetes Association guideline recommends considering aspirin use for primary prevention in adults with DM between ages 50 and 70 only after a risk vs benefit discussion of patient-specific bleeding risk factors and ASCVD risk-enhancing factors.¹⁰

Despite the demonstrated risks for bleeding with the routine use of aspirin, studies indicate that aspirin continues to be used commonly among older adults, often when unnecessary. In the 2017 National Health Interview Survey, about 23% of adults aged > 40 years in the United States without CVD used aspirin daily, and 23% of these did so without recommendation from a health care professional.¹¹ Furthermore, nearly half of adults ages ≥ 70 years and nearly one-quarter of adults with a history of peptic ulcer disease used aspirin daily.¹¹ Although the most recent guidelines from the ACC/AHA do not recommend a 10-year ASCVD risk threshold for therapy, one study illustrated that 12% of older adult patients were inappropriately prescribed aspirin for primary prevention despite a 10-year ASCVD risk of < 6%.^1,12 These studies highlight the large proportion of individuals, particularly older adults, who may be inappropriately taking aspirin for primary prevention.

Deprescribing Program

Deprescribing potentially inappropriate medications (PIMs) is particularly important in the older adult population, as these individuals experience a high risk of adverse effects (AEs), polypharmacy, cognitive decline, and falls related to medication use.^6,13-17 Evidence suggests that mortality outcomes are improved with the implementation of targeted deprescribing efforts based on patient-specific factors.¹⁸ Additionally, deprescribing unnecessary medications may improve adherence to other essential medications and reduce financial burdens.¹⁹ Pharmacists play a crucial role among health care professionals in the implementation of deprescribing practices, and studies have shown that physicians are highly accepting of pharmacists’ deprescribing recommendations.^13,20-22

Despite the evidence for the benefits of deprescribing, limited data are available regarding the impact and feasibility of a targeted aspirin deprescribing approach by nonphysician practitioners.²³ The objective of this study was to implement and evaluate the success of a pharmacist-driven aspirin deprescribing protocol for older adults in a primary care setting.

This aspirin deprescribing protocol was developed by ambulatory care clinical pharmacist or clinical pharmacist practitioners (CPPs), at the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. Within the US Department of Veterans Affairs (VA) health care system, CPPs work under a broad scope of practice with the ability to independently prescribe and monitor medications. The protocol was reviewed by physician stakeholders in both primary care and cardiology and a list was generated, including patients from 2 primary care panels aged ≥ 70 years with aspirin on their medication list, either as a prescription or over-the-counter medication, using the VA Information System Technology and Architecture. A CPP or supervised pharmacy intern identified patients from this list who were appropriate for risk/benefit discussions regarding the discontinuation of aspirin. Patients were excluded from the intervention if they had a history of clinical ASCVD, including myocardial infarction (MI), stable or unstable angina, coronary artery disease (CAD), coronary or other arterial revascularization, cerebrovascular accident (CVA), transient ischemic accident (TIA), or peripheral artery disease (PAD), or another documented indication for aspirin use, including pain, flushing (with niacin use), venous thromboembolism prophylaxis, valvular heart disease, or acute or recurrent pericarditis.

After identifying eligible patients, a CPP or pharmacy intern contacted patients by telephone, following a script to guide conversation. All patients were screened for potential appropriate aspirin indications, particularly any history of MI, CAD, CVA, TIA, PAD, or other clinical ASCVD. The patient was asked about their rationale for taking aspirin and patient-specific ASCVD risk-enhancing factors and bleeding risk factors and educated them on lifestyle modalities to reduce ASCVD risk, using the script as a guide. ASCVD risk-enhancing factors included family history of premature MI, inability to achieve BP goal, DM with the inability to achieve blood glucose or hemoglobin A_1c goal, tobacco use, or inadequate statin therapy. Bleeding risk factors included a history of gastrointestinal bleed or peptic ulcer disease, concurrent use of medications that increase bleeding risk, chronic kidney disease, or thrombocytopenia.

Through shared decision making with careful consideration of these factors, we reached a conclusion with each patient to either continue or to deprescribe aspirin. Each discussion was documented in the electronic health record (EHR) using a standard documentation template (eAppendix, available at doi:10.12788/fp.0320). The patient’s medication list also was updated to reflect changes in aspirin use. For patients who declined deprescribing, the CPP or pharmacy intern asked the patient for their primary reason for preferring to continue aspirin, which was subsequently categorized as one of the following: no prior concerns with bleeding, concerns about a future cardiovascular event, wishing to discuss further with their primary care practitioner (PCP), or identifying an appropriate use for aspirin not evident through record review. For the patients who wished to further discuss the issue with their PCP before deprescribing, the patient’s PCP was notified of this preference by a record alert to the note documenting the encounter, and the patient was also encouraged to follow up about this issue. A voicemail was left if the patient did not answer requesting a call back, and a second attempt was made within 2 weeks.

Data Collected

We collected data to assess the proportion of patients for whom aspirin for primary prevention was discontinued. For patients who declined deprescribing, we documented the rationale for continuing aspirin. Additionally, the feasibility of implementation was assessed, including pharmacist time spent on each record review and intervention. Descriptive statistics were generated to evaluate baseline characteristics and intervention outcomes. The time to completion of these tasks was summarized with descriptive statistics.

We reviewed 459 patient records, and 110 were determined eligible for risk/benefit discussions.

Results of the time-study analysis for each intervention indicated that a pharmacy intern or pharmacist spent about 2 minutes reviewing the record of each patient to determine eligibility for risk/benefit discussions. The 110 patients identified as eligible were 24% of the 459 records reviewed. An average (range) of 12 (6-20) minutes was spent on the telephone call plus documentation for each patient contacted. Additionally, we estimated that CPPs and pharmacy interns spent an approximate combined 12 hours in the development and review of materials for this program, including the protocol, script, and documentation templates. This also included about 1 hour to identify appropriate parameters for, and generate, the eligible patient list.

Discussion

The implementation of a pharmacist-driven aspirin deprescribing protocol for older adults in a primary care setting led to the discontinuation of inappropriate aspirin use in nearly half of older adults contacted. Furthermore, opportunities were identified to update medication lists to reflect previously self-discontinued aspirin for older adults. Just over one-quarter of those contacted declined to discontinue or reduce their aspirin dose. It is hypothesized that with these targeted deprescribing interventions, overall risk reduction for bleeding and polypharmacy will be observed for older adults.¹

In addition to deprescribing aspirin, CPPs used shared decision making to initiate risk/benefit discussions and to educate on targeted lifestyle modifications to lower ASCVD risk. While not all patients agreed to discontinue aspirin, all were provided education that may empower them to engage in future discussions with PCPs regarding appropriate aspirin use. Previous pharmacist-led deprescribing initiatives for proton pump inhibitors and other PIMs have indicated that a large percentage of patients who opt to further discuss a deprescribing concern with their PCPs ultimately resulted in deprescribing outcomes.^24,25 Additionally, a recent trial examining pharmacist-led deprescribing of 4 common PIMs in older adults compared the impact of pharmacists leading educational interventions directly to patients with pharmacists making deprescribing recommendations to physicians. Deprescribing was more successful when patients were involved in the decision-making process.²⁶

Limitations

Although this quality improvement initiative resulted in the deprescribing of inappropriate aspirin for many older adults, a limitation is the small sample size within a single institution. The population of male veterans also may limit generalizability to nonmale and nonveteran older adults. As the protocol was initiated within a limited number of primary care teams initially, future implementation into additional primary care teams will increase the number of older adults impacted by risk/benefit discussions regarding aspirin use. This work may not be generalizable to other health care systems. Many patients within the VA receive both their primary and specialty care within the system, which facilitates communication and collaboration between primary and specialty practitioners. The protocol may require workflow adjustments for patients receiving care within multiple systems. Additionally, although the deprescribing protocol was created in collaboration with physicians, CPPs within the VA work under a broad scope of practice that includes independent medication prescribing, deprescribing, and monitoring. This may be a consideration when implementing similar protocols at other sites, as collaborative practice agreements may need to be in place.

Future Directions

The time required to complete these interventions was generally feasible, though this intervention would require some workflow alteration to be incorporated routinely into a CPP’s schedule. The telephone calls were completed as isolated interventions and were not incorporated into existing scheduled primary care appointments. In the future, the aspirin deprescribing protocol could be incorporated into existing pharmacist-led primary care appointments. Based on the outcomes of this study, CPPs are leading an initiative to develop an aspirin deprescribing clinical reminder tool, which may be quickly inserted into a progress note within the EHR and may be incorporated into any primary care visit led by a CPP or PCP.

Conclusions

This study demonstrates that a pharmacist-led aspirin deprescribing protocol in the ambulatory care pharmacy setting was successful in the discontinuation of unnecessary aspirin use in older adults. The protocol also provided opportunities for education on ASCVD risk reduction in all older adults reached. These findings highlight the role of pharmacists in deprescribing PIMs for older adults and identifying opportunities to further streamline risk/benefit discussions on aspirin deprescribing potential within primary care visits.

In 2019, diabetes mellitus (DM) was the seventh leading cause of death in the United States, and currently, about 11% of the American population has a DM diagnosis.¹ Most have a diagnosis of type 2 diabetes (T2DM), which has a strong genetic predisposition, and the risk of developing T2DM increases with age, obesity, and lack of physical activity.^1,2 Nearly one-quarter of veterans have a diagnosis of DM, and DM is the leading cause of comorbidities, such as blindness, end-stage renal disease, and amputation for patients receiving care from the Veterans Health Administration (VHA).² The elevated incidence of DM in the veteran population is attributed to a variety of factors, including exposure to herbicides, such as Agent Orange, advanced age, increased risk of obesity, and limited access to high-quality food.³

After diagnosis, both the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) emphasize the appropriate use of lifestyle management and pharmacologic therapy for DM care. The use of pharmacologic agents (oral medications, insulin, or noninsulin injectables) is often determined by efficacy, cost, potential adverse effects (AEs), and patient factors and comorbidities.^4,5

The initial recommendation for pharmacologic treatment for T2DM differs slightly between expert guidelines. The ADA and AACE/ACE recommend any of the following as initial monotherapy, listed in order to represent a hierarchy of usage: metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 (SGLT-2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors, with the first 3 agents carrying the strongest recommendations.^4,5 For patients with established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure, it is recommended to start a long-acting GLP-1 RA or SGLT-2 inhibitor. For patients with T2DM and hemoglobin A_1c (HbA_1c) between 7.5% and 9.0% at diagnosis, the AACE/ACE recommend initiation of dual therapy using metformin alongside another first-line agent and recommend the addition of another antidiabetic agent if glycemic goals are not met after regular follow-up. AACE/ACE recommend the consideration of insulin therapy in symptomatic patients with HbA_1c > 9.0%.⁵ In contrast, the ADA recommends metformin as first-line therapy for all patients with T2DM and recommends dual therapy using metformin and another preferred agent (selection based on comorbidities) when HbA_1c is 1.5% to 2% above target. The ADA recommends the consideration of insulin with HbA_1c > 10% or with evidence of ongoing catabolism or symptoms of hyperglycemia.⁴ There are several reasons why insulin may be initiated prior to GLP-1 RAs, including profound hyperglycemia at time of diagnosis or implementation of insulin agents prior to commercial availability of GLP-1 RA.

GLP-1 RAs are analogs of the hormone incretin, which increases glucose-dependent insulin secretion, decreases postprandial glucagon secretion, increases satiety, and slows gastric emptying.^6,7 When used in combination with noninsulin agents, GLP-1 RAs have demonstrated HbA_1c reductions of 0.5% to 1.5%.⁸ The use of GLP-1 RAs with basal insulin also has been studied extensively.^6,8-10 When the combination of GLP-1 RAs and basal insulin was compared with basal/bolus insulin regimens, the use of the GLP-1 RAs resulted in lower HbA_1c levels and lower incidence of hypoglycemia.^6,9 Data have demonstrated the complementary mechanisms of using basal insulin and GLP 1 RAs in decreasing HbA_1c levels, insulin requirements, and weight compared with using basal insulin monotherapy and basal/bolus combinations.^6,9-13 Moreover, 3 GLP-1 RA medications currently on the market (liraglutide, dulaglutide, and semaglutide) have displayed cardiovascular and renal benefits, further supporting the use of these medications.^2,5

Despite these benefits, GLP-1 RAs may have bothersome AEs and are associated with a high cost.⁶ In addition, some studies have found that as the length of therapy increases, the positive effects of these agents may diminish.^9,11 In one study, which looked at the impact of the addition of exenatide to patients taking basal or basal/bolus insulin regimens, mean changes in weight were −2.4 kg at 0 to 6 months, −4.3 kg at 6 to 12 months, −6.2 kg at 12 to 18 months, and −5.5 kg at 18 to 27 months. After 18 months, an increase in weight was observed, but the increase remained lower than baseline.¹¹ Another study, conducted over 12 months, found no significant decrease in weight or total daily dose (TDD) of insulin when exenatide or liraglutide were added to various insulin regimens (basal or basal/bolus).¹³ To date, minimal published data exist regarding the addition of newer GLP-1 RAs and the long-term use of these agents beyond 12 months in patients taking basal/bolus insulin regimens. The primary goal of this study was to evaluate the effect of adding GLP-1 RAs to basal/bolus insulin regimens over a 24-month period.

Methods

This study was a retrospective, electronic health record review of all patients on basal and bolus insulin regimens who received additional therapy with a GLP-1 RA at Veteran Health Indiana in Indianapolis from September 1, 2015, to June 30, 2019. Patients meeting inclusion criteria served as their own control. The primary outcome was change in HbA_1c at 3, 6, 12, 18, and 24 months after initiation of the GLP-1 RA. Secondary outcomes included change in weight and TDD of insulin at 3, 6, 12, 18, and 24 months after the initiation of the GLP-1 RAs and incidence of patient-reported or laboratory-confirmed hypoglycemia and other AEs.

Patients were included if they were aged ≥ 18 years with a diagnosis of T2DM, had concomitant prescriptions for both a basal insulin (glargine, detemir, or NPH) and a bolus insulin (aspart, lispro, or regular) before receiving add-on therapy with a GLP-1 RA (exenatide, liraglutide, albiglutide, lixisenatide, dulaglutide, or semaglutide) from September 1, 2015, to June 30, 2019, and had baseline and subsequent HbA_1c measurements available in the electronic health record. Patients were excluded if they had a diagnosis of type 1 DM (T1DM), were followed by an outside clinician for DM care, or if the GLP-1 RA was discontinued before subsequent HbA_1c measurement. The study protocol was approved by the Research and Development Office of Veteran Health Indiana, and the project was deemed exempt from review by the Indiana University Institutional Review Board due to the retrospective nature of the study.

Data analysis was performed using Excel. Change from baseline for each interval was computed, and 1 sample t tests (2-tailed) compared change from baseline to no change. Due to the disparity in the number of patients with data available at each of the time intervals, a mean plot was presented for each group of patients within each interval, allowing mean changes in individual groups to be observed over time.

Results

One hundred twenty-three subjects met inclusion criteria; 16 patients were excluded due to GLP-1 RA discontinuation before follow-up measurement of HbA_1c; 14 were excluded due to patients being managed by a clinician outside of the facility; 1 patient was excluded for lack of documentation regarding baseline and subsequent insulin doses. Ninety-two patient charts were reviewed. Participants had a mean age of 64 years, 95% were male, and 89% were White. Mean baseline HbA_1c was 9.2%, mean body mass index was 38.9, and the mean TDD of insulin was 184 units.

Since some patients switched between GLP-1 RAs throughout the study and there was variation in timing of laboratory and clinic follow-up,

Discussion

Adding a GLP-1 RA to basal/bolus insulin regimens was associated with a statistically significant decrease in HbA_1c at each time point through 18 months. The greatest improvement in glycemic control from baseline was seen at 3 months, with improvements in HbA_1c diminishing at each subsequent period. The study also demonstrated a significant decrease in weight at each time point through 18 months. The greatest decrease in weight was observed at both 6 and 12 months. Statistically significant decreases in TDD were observed at 3, 6, and 12 months. Insulin changes after 12 months were not found to be statistically significant.

Few studies have previously evaluated the use of GLP-1 RAs in patients with T2DM who are already taking basal/bolus insulin regimens. Gyorffy and colleagues reported significant improvements in glycemic control at 3 and 6 months in a sample of 54 patients taking basal/bolus insulin when liraglutide or exenatide was added, although statistical significance was not found at the final 12-month time point.¹³ That study also found a significant decrease in weight at 6 months; however there was not a significant reduction in weight at both 3 and 12 months of GLP-1 RA therapy. There was not a significant decrease in TDD at any of the collected time points. Nonetheless, Gyorffy and colleagues concluded that reduction in TDD leveled off after 12 months, which is consistent with this study’s findings. The small size of the study may have limited the ability to detect statistical significance; however, this study was conducted in a population that was racially diverse and included a higher proportion of women, though average age was similar.¹³

Yoon and colleagues reported weight loss through 18 months, then saw weight increase, though weights did remain lower than baseline. The study also showed no significant change in TDD of insulin after 12 months of concomitant exenatide and insulin therapy.¹¹ Although these results mirror the outcomes observed in this study, Yoon and colleagues did not differentiate results between basal and basal/bolus insulin groups.¹¹ Seino and colleagues observed no significant change in weight after 36 weeks of GLP-1 RA therapy in Japanese patients when used with basal and basal/bolus insulin regimens. Despite the consideration that the population in the study was not overweight (mean body mass index was 25.6), the results of these studies support the idea that effects of GLP-1 RAs on weight and TDD may diminish over time.¹⁴

Within the VHA, GLP-1 RAs are nonformulary medications. Patients must meet certain criteria in order to be approved for these agents, which may include diagnosis of CVD, renal disease, or failure to reach glycemic control with the use of oral agents or insulin. Therefore, participants of this study represent a particular subset of VHA patients, many of whom may have been selected for consideration due to long-standing or uncontrolled T2DM and failure of previous therapies. The baseline demographics support this idea, given poor glycemic control at baseline and high insulin requirements. Once approved for GLP-1 RA therapy, semaglutide is currently the preferred agent within the VHA, with other agents available for select considerations. It should be noted that albiglutide, which was the primary agent selected for some of the patients included in this study, was removed from the market in 2017 for economic considerations.¹⁵ In the case for these patients, a conversion to a formulary-preferred GLP-1 RA was made.

Most of the patients included in this study (70%) were maintained on metformin from baseline throughout the study period. Fifty-seven percent of patients were taking TDD of insulin > 150 units. Considering the significant cost of concentrated insulins, the addition of GLP-1 RAs to standard insulin may prove to be beneficial from a cost standpoint. Additional research in this area may be warranted to establish more data regarding this potential benefit of GLP-1 RAs as add-on therapy.

Many adverse drug reactions were reported at different periods; however, most of these were associated with the gastrointestinal system, which is consistent with current literature, drug labeling, and the mechanism of action.¹⁶ Hypoglycemia occurred in about one-third of the participants; however, it should be noted that alone, GLP-1 RAs are not associated with a high risk of hypoglycemia. Previous studies have found that GLP-1 RA monotherapy is associated with hypoglycemia in 1.6% to 12.6% of patients.^17,18 More likely, the combination of basal/bolus insulin and the GLP-1 RA’s effect on increasing insulin sensitivity through weight loss, improving glucose-dependent insulin secretion, or by decreasing appetite and therefore decreasing carbohydrate intake contributed to the hypoglycemia prevalence.

Limitations and Strengths

Limitations of this study include a small patient population and a gradual reduction in available data as time periods progressed, making even smaller sample sizes for subsequent time periods. A majority of participants were older, males and White race. This could have limited the determination of statistical significance and applicability of the results to other patient populations. Another potential limitation was the retrospective nature of the study design, which may have limited reporting of hypoglycemia and other AEs based on the documentation of the clinician.

Strengths included the study duration and the diversity of GLP-1 RAs used by participants, as the impact of many of these agents has not yet been assessed in the literature. In addition, the retrospective nature of the study allows for a more realistic representation of patient adherence, education, and motivation, which are likely different from those of patients included in prospective clinical trials.

There are no clear guidelines dictating the optimal duration of concomitant GLP-1 RA and insulin therapy; however, our study suggests that there may be continued benefits past short-term use. Also our study suggests that patients with T2DM treated with basal/bolus insulin regimens may glean additional benefit from adding GLP-1 RAs; however, further randomized, controlled studies are warranted, particularly in poorly controlled patients requiring even more aggressive treatment regimens, such as concentrated insulins.

Conclusions

In our study, adding GLP-1 RA to basal/bolus insulin was associated with a significant decrease in HbA_1c from baseline through 18 months. An overall decrease in weight and TDD of insulin was observed through 24 months, but the change in weight was not significant past 18 months, and the change in insulin requirement was not significant past 12 months. Hypoglycemia was observed in almost one-third of patients, and gastrointestinal symptoms were the most common AE observed as a result of adding GLP-1 RAs. More studies are needed to better evaluate the durability and cost benefit of GLP-1 RAs, especially in patients with high insulin requirements.

Acknowledgments

This material is the result of work supported with resources and facilities at Veteran Health Indiana in Indianapolis. Study data were collected and managed using REDCap electronic data capture tools hosted at Veteran Health Indiana. The authors also acknowledge George Eckert for his assistance with data analysis.