Pharmacology

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

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

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

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

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

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

Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.

The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.

The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.

“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”

If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
 

Not enough data to support a change in practice

The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.

“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.

“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.

“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”

First-choice therapy for acid-related disorders

PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.

However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.

To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.

Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).

The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.

Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.

Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.

Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).

The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.

Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.

The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.

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

Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.

The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.

The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.

“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”

If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
 

Not enough data to support a change in practice

The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.

“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.

“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.

“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”

First-choice therapy for acid-related disorders

PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.

However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.

To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.

Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).

The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.

Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.

Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.

Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).

The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.

Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.

The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.

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

Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.

The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.

The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.

“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”

If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
 

Not enough data to support a change in practice

The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.

“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.

“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.

“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”

First-choice therapy for acid-related disorders

PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.

However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.

To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.

Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).

The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.

Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.

Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.

Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).

The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.

Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.

The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.

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

Higher levels of specific carotenoid antioxidants in blood may help guard against age-related dementia, new research suggests.

Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.

Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.

“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release. 

“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.

“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.

The study was published online in Neurology.
 

Reduced dementia risk

The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.

They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.

They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.

For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.

Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.

For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).

This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.

No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.

Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.

“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.

“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
 

An important step forward

In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”

This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.

The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.

However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.

They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.

“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.

The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.

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

Higher levels of specific carotenoid antioxidants in blood may help guard against age-related dementia, new research suggests.

Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.

Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.

“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release. 

“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.

“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.

The study was published online in Neurology.
 

Reduced dementia risk

The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.

They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.

They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.

For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.

Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.

For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).

This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.

No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.

Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.

“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.

“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
 

An important step forward

In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”

This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.

The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.

However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.

They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.

“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.

The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.

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

Higher levels of specific carotenoid antioxidants in blood may help guard against age-related dementia, new research suggests.

Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.

Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.

“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release. 

“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.

“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.

The study was published online in Neurology.
 

Reduced dementia risk

The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.

They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.

They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.

For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.

Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.

For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).

This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.

No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.

Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.

“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.

“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
 

An important step forward

In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”

This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.

The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.

However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.

They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.

“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.

The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.

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

Topline results from the phase 3 DELIVER trial show dapagliflozin (Farxiga) significantly reduced the primary endpoint of cardiovascular death or worsening heart failure in patients with mildly reduced or preserved ejection fraction, AstraZeneca announced today.

The sodium-glucose cotransporter 2 (SGLT2) inhibitor is not approved in this setting but is already approved for treatment of type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction.

“The results of DELIVER extend the benefit of dapagliflozin to the full spectrum of patients with heart failure,” principal investigator of the trial, Scott Solomon, MD, Harvard Medical School and Brigham and Women’s Hospital, Boston, said in the news release.

The safety and tolerability of dapagliflozin in the trial were consistent with its established safety profile, the company says.

The full trial results will be submitted for presentation at a forthcoming medical meeting, and regulatory submissions will be made in the coming months, it notes.

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

Topline results from the phase 3 DELIVER trial show dapagliflozin (Farxiga) significantly reduced the primary endpoint of cardiovascular death or worsening heart failure in patients with mildly reduced or preserved ejection fraction, AstraZeneca announced today.

The sodium-glucose cotransporter 2 (SGLT2) inhibitor is not approved in this setting but is already approved for treatment of type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction.

“The results of DELIVER extend the benefit of dapagliflozin to the full spectrum of patients with heart failure,” principal investigator of the trial, Scott Solomon, MD, Harvard Medical School and Brigham and Women’s Hospital, Boston, said in the news release.

The safety and tolerability of dapagliflozin in the trial were consistent with its established safety profile, the company says.

The full trial results will be submitted for presentation at a forthcoming medical meeting, and regulatory submissions will be made in the coming months, it notes.

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

Topline results from the phase 3 DELIVER trial show dapagliflozin (Farxiga) significantly reduced the primary endpoint of cardiovascular death or worsening heart failure in patients with mildly reduced or preserved ejection fraction, AstraZeneca announced today.

The sodium-glucose cotransporter 2 (SGLT2) inhibitor is not approved in this setting but is already approved for treatment of type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction.

“The results of DELIVER extend the benefit of dapagliflozin to the full spectrum of patients with heart failure,” principal investigator of the trial, Scott Solomon, MD, Harvard Medical School and Brigham and Women’s Hospital, Boston, said in the news release.

The safety and tolerability of dapagliflozin in the trial were consistent with its established safety profile, the company says.

The full trial results will be submitted for presentation at a forthcoming medical meeting, and regulatory submissions will be made in the coming months, it notes.

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

The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.

Dacarbazine, an essential part of the four-drug standard of care for managing Hodgkin lymphoma, has been in short supply since last summer, prompting experts to search for a viable substitute.

In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.

Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.

Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.

In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.

“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.

According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
 

Finding a substitute

In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.

The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.

The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?

For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.

The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.

For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.

Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.

For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.

The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).

For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).

For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.

Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”

To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.

For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.

Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.

The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.

No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.

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

The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.

Dacarbazine, an essential part of the four-drug standard of care for managing Hodgkin lymphoma, has been in short supply since last summer, prompting experts to search for a viable substitute.

In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.

Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.

Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.

In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.

“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.

According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
 

Finding a substitute

In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.

The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.

The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?

For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.

The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.

For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.

Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.

For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.

The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).

For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).

For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.

Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”

To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.

For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.

Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.

The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.

No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.

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

The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.

Dacarbazine, an essential part of the four-drug standard of care for managing Hodgkin lymphoma, has been in short supply since last summer, prompting experts to search for a viable substitute.

In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.

Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.

Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.

In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.

“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.

According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
 

Finding a substitute

In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.

The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.

The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?

For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.

The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.

For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.

Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.

For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.

The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).

For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).

For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.

Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”

To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.

For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.

Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.

The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.

No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.

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

Seven physicians were among 12 medical professionals charged today by the U.S. Department of Justice with opioid distribution offenses.

In coordination with federal and state law enforcement, the DOJ charged the defendants for their involvement in the illegal distribution of opioids. At the time that they were charged with the alleged offenses, 12 of the defendants were medical professionals.

The 12 persons in eight federal districts across the country distributed more than 115 million controlled substances, including buprenorphine, clonazepam, dextroamphetamine-amphetamine, hydrocodone, morphine sulfate, oxycodone, oxymorphone, and Suboxone, per the DOJ.

“Doctors and health care professionals are entrusted with prescribing medicine responsibly and in the best interests of their patients. Today’s takedown targets medical providers across the country whose greed drove them to abandon this responsibility in favor of criminal profits,” said Anne Milgram, administrator of the Drug Enforcement Administration.
 

Medical professionals, others across six states charged

One former nurse, one business manager, and one individual who practiced medicine without a medical credential are among those listed in the indictment. These include the following:

• Eskender Getachew, MD, a Columbus, Ohio, sleep medicine specialist, was charged with unlawful distribution of controlled substances outside the use of professional practice and not for a legitimate medical practice.
• Charles Kistler, DO, an Upper Arlington, Ohio, family practice physician, was charged with unlawful distribution of controlled substances for unlawful prescribing at Midtown Family Practice Clinic in Columbus.
• Yogeshwar Gil, MBBS, a Manchester, Tenn., family medicine doctor and owner of a medical practice, was charged with conspiracy to unlawfully distribute controlled substances and maintaining a drug-involved premises. Dr. Gil was charged in connection with an alleged scheme to distribute opioids and Suboxone outside the usual course of professional practice and without a legitimate medical purpose.
• Contessa Holley, RN, a Pulaski, Tenn., former nurse and clinical director, was charged with wire fraud, aggravated identity theft, and possession of a controlled substance with intent to distribute. She’s alleged to be connected with a scheme to unlawfully obtain opioids by filling fraudulent prescriptions in the names of current and former patients who were in hospice. The indictment alleged that Ms. Holley used the patients’ hospice benefits to cover the opioids’ costs while keeping the drugs for her own use and for further distribution.
• Francene Aretha Gayle, MD, an Orlando, Fla., physician, was charged with conspiracy to unlawfully distribute controlled substances, conspiracy to commit health care fraud, health care fraud, and several substantive counts of illegally issuing opioid prescriptions. Dr. Gayle was charged along with Schara Monique Davis, a Huntsville, Ala.–based business manager. Per the indictment, Dr. Gayle and Ms. Davis operated three medical clinics in Alabama, where Dr. Gayle was the sole physician. The medical clinics billed health insurers for millions of dollars in patient visits that Dr. Gayle had supposedly conducted but during which she was allegedly absent from the clinics; other staff members conducted the visits instead. It’s alleged that Dr. Gayle presigned prescriptions for opioids that were given to patients.
• Robert Taffet, MD, a Haddonfield, N.J., orthopedic surgeon and owner of a medical practice in Sicklerville, N.J., was charged with conspiracy to unlawfully distribute controlled substances. The indictment alleges that he falsified patient files to state that he interacted with patients when he didn’t and that he issued prescriptions for opioids and other controlled substances without assessing the patients in person or by telemedicine. It’s alleged that Dr. Taffett issued prescriptions for more than 179,000 pills that were dispensed by New Jersey pharmacies between April 2020 and December 2021.
• Hau La, MD, a Brentwood, Tenn., family medicine physician and the operator of Absolute Medical Care in Smyrna, Tenn., was charged with sixteen counts of unlawful distribution of a controlled substance. The physician is alleged to have unlawfully prescribed opioids to eight patients outside the usual course of practice and without a legitimate medical purpose.
• Frederick De Mesa, of War, W.Va., practiced as a physician and used a DEA registration number that allowed him to prescribe controlled substances. Mr. De Mesa prescribed these substances without a medical license and didn’t have an active DEA registration number, according to the indictment.
• Loey Kousa, a former internist from Paintsville, Ky., was charged with unlawful distribution of controlled substances, healthcare fraud, and making false statements in connection with the delivery of health care services. The indictment alleges that the former physician issued prescriptions for opioids outside the usual course of professional practice and without a legitimate medical purpose in his capacity as owner and operator of East KY Clinic in Paintsville. He is alleged to have issued the unlawful prescriptions for patients whose treatments were covered by taxpayer-funded programs such as Medicare and Medicaid; he also billed these programs for medically unnecessary procedures for these patients.

Also included in the indictment were Jay Sadrinia, DMD, a Villa Hills, Ky., dentist, who was charged with four counts of illegal distribution of oxycodone and morphine sulfate and one count of illegal distribution of morphine sulfate that resulted in death or serious bodily injury; and Casey Kelleher, an owner-operator of Neighborhood Pharmacy in Boynton Beach, Fla., who allegedly sold large amounts of oxycodone and hydromorphone on the black market.

The Centers for Medicare & Medicaid Services’ Center for Program Integrity has taken six administrative actions against health care providers for their alleged involvement in these offenses, per the DOJ’s announcement.

“Patient care and safety are top priorities for us, and CMS has taken administrative action against six providers to protect critical resources entrusted to Medicare while also safeguarding people with Medicare,” said CMS Administrator Chiquita Brooks-LaSure.

“These actions to combat fraud, waste, and abuse in our federal programs would not be possible without the close and successful partnership of the Centers for Medicare & Medicaid Services, the Department of Justice, and the U.S. Department of Health and Human Services Office of Inspector General,” she added.

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

Seven physicians were among 12 medical professionals charged today by the U.S. Department of Justice with opioid distribution offenses.

In coordination with federal and state law enforcement, the DOJ charged the defendants for their involvement in the illegal distribution of opioids. At the time that they were charged with the alleged offenses, 12 of the defendants were medical professionals.

The 12 persons in eight federal districts across the country distributed more than 115 million controlled substances, including buprenorphine, clonazepam, dextroamphetamine-amphetamine, hydrocodone, morphine sulfate, oxycodone, oxymorphone, and Suboxone, per the DOJ.

“Doctors and health care professionals are entrusted with prescribing medicine responsibly and in the best interests of their patients. Today’s takedown targets medical providers across the country whose greed drove them to abandon this responsibility in favor of criminal profits,” said Anne Milgram, administrator of the Drug Enforcement Administration.
 

Medical professionals, others across six states charged

One former nurse, one business manager, and one individual who practiced medicine without a medical credential are among those listed in the indictment. These include the following:

• Eskender Getachew, MD, a Columbus, Ohio, sleep medicine specialist, was charged with unlawful distribution of controlled substances outside the use of professional practice and not for a legitimate medical practice.
• Charles Kistler, DO, an Upper Arlington, Ohio, family practice physician, was charged with unlawful distribution of controlled substances for unlawful prescribing at Midtown Family Practice Clinic in Columbus.
• Yogeshwar Gil, MBBS, a Manchester, Tenn., family medicine doctor and owner of a medical practice, was charged with conspiracy to unlawfully distribute controlled substances and maintaining a drug-involved premises. Dr. Gil was charged in connection with an alleged scheme to distribute opioids and Suboxone outside the usual course of professional practice and without a legitimate medical purpose.
• Contessa Holley, RN, a Pulaski, Tenn., former nurse and clinical director, was charged with wire fraud, aggravated identity theft, and possession of a controlled substance with intent to distribute. She’s alleged to be connected with a scheme to unlawfully obtain opioids by filling fraudulent prescriptions in the names of current and former patients who were in hospice. The indictment alleged that Ms. Holley used the patients’ hospice benefits to cover the opioids’ costs while keeping the drugs for her own use and for further distribution.
• Francene Aretha Gayle, MD, an Orlando, Fla., physician, was charged with conspiracy to unlawfully distribute controlled substances, conspiracy to commit health care fraud, health care fraud, and several substantive counts of illegally issuing opioid prescriptions. Dr. Gayle was charged along with Schara Monique Davis, a Huntsville, Ala.–based business manager. Per the indictment, Dr. Gayle and Ms. Davis operated three medical clinics in Alabama, where Dr. Gayle was the sole physician. The medical clinics billed health insurers for millions of dollars in patient visits that Dr. Gayle had supposedly conducted but during which she was allegedly absent from the clinics; other staff members conducted the visits instead. It’s alleged that Dr. Gayle presigned prescriptions for opioids that were given to patients.
• Robert Taffet, MD, a Haddonfield, N.J., orthopedic surgeon and owner of a medical practice in Sicklerville, N.J., was charged with conspiracy to unlawfully distribute controlled substances. The indictment alleges that he falsified patient files to state that he interacted with patients when he didn’t and that he issued prescriptions for opioids and other controlled substances without assessing the patients in person or by telemedicine. It’s alleged that Dr. Taffett issued prescriptions for more than 179,000 pills that were dispensed by New Jersey pharmacies between April 2020 and December 2021.
• Hau La, MD, a Brentwood, Tenn., family medicine physician and the operator of Absolute Medical Care in Smyrna, Tenn., was charged with sixteen counts of unlawful distribution of a controlled substance. The physician is alleged to have unlawfully prescribed opioids to eight patients outside the usual course of practice and without a legitimate medical purpose.
• Frederick De Mesa, of War, W.Va., practiced as a physician and used a DEA registration number that allowed him to prescribe controlled substances. Mr. De Mesa prescribed these substances without a medical license and didn’t have an active DEA registration number, according to the indictment.
• Loey Kousa, a former internist from Paintsville, Ky., was charged with unlawful distribution of controlled substances, healthcare fraud, and making false statements in connection with the delivery of health care services. The indictment alleges that the former physician issued prescriptions for opioids outside the usual course of professional practice and without a legitimate medical purpose in his capacity as owner and operator of East KY Clinic in Paintsville. He is alleged to have issued the unlawful prescriptions for patients whose treatments were covered by taxpayer-funded programs such as Medicare and Medicaid; he also billed these programs for medically unnecessary procedures for these patients.

Also included in the indictment were Jay Sadrinia, DMD, a Villa Hills, Ky., dentist, who was charged with four counts of illegal distribution of oxycodone and morphine sulfate and one count of illegal distribution of morphine sulfate that resulted in death or serious bodily injury; and Casey Kelleher, an owner-operator of Neighborhood Pharmacy in Boynton Beach, Fla., who allegedly sold large amounts of oxycodone and hydromorphone on the black market.

The Centers for Medicare & Medicaid Services’ Center for Program Integrity has taken six administrative actions against health care providers for their alleged involvement in these offenses, per the DOJ’s announcement.

“Patient care and safety are top priorities for us, and CMS has taken administrative action against six providers to protect critical resources entrusted to Medicare while also safeguarding people with Medicare,” said CMS Administrator Chiquita Brooks-LaSure.

“These actions to combat fraud, waste, and abuse in our federal programs would not be possible without the close and successful partnership of the Centers for Medicare & Medicaid Services, the Department of Justice, and the U.S. Department of Health and Human Services Office of Inspector General,” she added.

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

Seven physicians were among 12 medical professionals charged today by the U.S. Department of Justice with opioid distribution offenses.

In coordination with federal and state law enforcement, the DOJ charged the defendants for their involvement in the illegal distribution of opioids. At the time that they were charged with the alleged offenses, 12 of the defendants were medical professionals.

The 12 persons in eight federal districts across the country distributed more than 115 million controlled substances, including buprenorphine, clonazepam, dextroamphetamine-amphetamine, hydrocodone, morphine sulfate, oxycodone, oxymorphone, and Suboxone, per the DOJ.

“Doctors and health care professionals are entrusted with prescribing medicine responsibly and in the best interests of their patients. Today’s takedown targets medical providers across the country whose greed drove them to abandon this responsibility in favor of criminal profits,” said Anne Milgram, administrator of the Drug Enforcement Administration.
 

Medical professionals, others across six states charged

One former nurse, one business manager, and one individual who practiced medicine without a medical credential are among those listed in the indictment. These include the following:

• Eskender Getachew, MD, a Columbus, Ohio, sleep medicine specialist, was charged with unlawful distribution of controlled substances outside the use of professional practice and not for a legitimate medical practice.
• Charles Kistler, DO, an Upper Arlington, Ohio, family practice physician, was charged with unlawful distribution of controlled substances for unlawful prescribing at Midtown Family Practice Clinic in Columbus.
• Yogeshwar Gil, MBBS, a Manchester, Tenn., family medicine doctor and owner of a medical practice, was charged with conspiracy to unlawfully distribute controlled substances and maintaining a drug-involved premises. Dr. Gil was charged in connection with an alleged scheme to distribute opioids and Suboxone outside the usual course of professional practice and without a legitimate medical purpose.
• Contessa Holley, RN, a Pulaski, Tenn., former nurse and clinical director, was charged with wire fraud, aggravated identity theft, and possession of a controlled substance with intent to distribute. She’s alleged to be connected with a scheme to unlawfully obtain opioids by filling fraudulent prescriptions in the names of current and former patients who were in hospice. The indictment alleged that Ms. Holley used the patients’ hospice benefits to cover the opioids’ costs while keeping the drugs for her own use and for further distribution.
• Francene Aretha Gayle, MD, an Orlando, Fla., physician, was charged with conspiracy to unlawfully distribute controlled substances, conspiracy to commit health care fraud, health care fraud, and several substantive counts of illegally issuing opioid prescriptions. Dr. Gayle was charged along with Schara Monique Davis, a Huntsville, Ala.–based business manager. Per the indictment, Dr. Gayle and Ms. Davis operated three medical clinics in Alabama, where Dr. Gayle was the sole physician. The medical clinics billed health insurers for millions of dollars in patient visits that Dr. Gayle had supposedly conducted but during which she was allegedly absent from the clinics; other staff members conducted the visits instead. It’s alleged that Dr. Gayle presigned prescriptions for opioids that were given to patients.
• Robert Taffet, MD, a Haddonfield, N.J., orthopedic surgeon and owner of a medical practice in Sicklerville, N.J., was charged with conspiracy to unlawfully distribute controlled substances. The indictment alleges that he falsified patient files to state that he interacted with patients when he didn’t and that he issued prescriptions for opioids and other controlled substances without assessing the patients in person or by telemedicine. It’s alleged that Dr. Taffett issued prescriptions for more than 179,000 pills that were dispensed by New Jersey pharmacies between April 2020 and December 2021.
• Hau La, MD, a Brentwood, Tenn., family medicine physician and the operator of Absolute Medical Care in Smyrna, Tenn., was charged with sixteen counts of unlawful distribution of a controlled substance. The physician is alleged to have unlawfully prescribed opioids to eight patients outside the usual course of practice and without a legitimate medical purpose.
• Frederick De Mesa, of War, W.Va., practiced as a physician and used a DEA registration number that allowed him to prescribe controlled substances. Mr. De Mesa prescribed these substances without a medical license and didn’t have an active DEA registration number, according to the indictment.
• Loey Kousa, a former internist from Paintsville, Ky., was charged with unlawful distribution of controlled substances, healthcare fraud, and making false statements in connection with the delivery of health care services. The indictment alleges that the former physician issued prescriptions for opioids outside the usual course of professional practice and without a legitimate medical purpose in his capacity as owner and operator of East KY Clinic in Paintsville. He is alleged to have issued the unlawful prescriptions for patients whose treatments were covered by taxpayer-funded programs such as Medicare and Medicaid; he also billed these programs for medically unnecessary procedures for these patients.

Also included in the indictment were Jay Sadrinia, DMD, a Villa Hills, Ky., dentist, who was charged with four counts of illegal distribution of oxycodone and morphine sulfate and one count of illegal distribution of morphine sulfate that resulted in death or serious bodily injury; and Casey Kelleher, an owner-operator of Neighborhood Pharmacy in Boynton Beach, Fla., who allegedly sold large amounts of oxycodone and hydromorphone on the black market.

The Centers for Medicare & Medicaid Services’ Center for Program Integrity has taken six administrative actions against health care providers for their alleged involvement in these offenses, per the DOJ’s announcement.

“Patient care and safety are top priorities for us, and CMS has taken administrative action against six providers to protect critical resources entrusted to Medicare while also safeguarding people with Medicare,” said CMS Administrator Chiquita Brooks-LaSure.

“These actions to combat fraud, waste, and abuse in our federal programs would not be possible without the close and successful partnership of the Centers for Medicare & Medicaid Services, the Department of Justice, and the U.S. Department of Health and Human Services Office of Inspector General,” she added.

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

Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?   

Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.   

All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?

Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.

Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”

“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
 

Rampant misuse

Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.

“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.

“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”

The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
 

How to be a better steward

The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.

All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.

Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”

Clinicians should also:

• Observe antibiotic best practices
• Optimize antibiotic selection and dosing
• Practice effective diagnostic stewardship
• Use the shortest duration of therapy necessary
• Avoid antibiotics for inappropriate indications
• Educate patients on when antibiotics are needed
• Follow and become good antibiotic stewardship mentors

“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”

Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.

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

Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?   

Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.   

All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?

Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.

Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”

“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
 

Rampant misuse

Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.

“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.

“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”

The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
 

How to be a better steward

The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.

All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.

Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”

Clinicians should also:

• Observe antibiotic best practices
• Optimize antibiotic selection and dosing
• Practice effective diagnostic stewardship
• Use the shortest duration of therapy necessary
• Avoid antibiotics for inappropriate indications
• Educate patients on when antibiotics are needed
• Follow and become good antibiotic stewardship mentors

“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”

Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.

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

Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?   

Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.   

All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?

Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.

Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”

“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
 

Rampant misuse

Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.

“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.

“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”

The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
 

How to be a better steward

The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.

All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.

Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”

Clinicians should also:

• Observe antibiotic best practices
• Optimize antibiotic selection and dosing
• Practice effective diagnostic stewardship
• Use the shortest duration of therapy necessary
• Avoid antibiotics for inappropriate indications
• Educate patients on when antibiotics are needed
• Follow and become good antibiotic stewardship mentors

“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”

Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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