NATIONAL HARBOR, MD. – Treatment guidelines are helpful in treating relapsing-remitting multiple sclerosis (RRMS), a neurologist told colleagues, but they’re only useful to an extent. Consider his 40-year-old female patient who’s averse to vaccines, often misses appointments, and seems to be unable to take blood pressure drugs as prescribed. In this case, the best strategy may not be the drug with the highest efficacy.

“There’s no pharmaceutical insert that’s going to tell you what to do with all of this information,” John R. Rinker II, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s important to not only know about the disease and the specifics of the pharmaceuticals, but also about the patient’s personal circumstances, their comorbidities, their social situation, and how it all ties together.”

Fortunately, he said, there are about two dozen medication options now available for RRMS. Noting that his scale is at best “a crude approximation of reality,” he said their efficacy runs the gamut from low (glatiramer acetate and beta-interferons) to high (cladribine, alemtuzumab). He places sphingosine-1 phosphate (SIP1) modulators in the mid-range in terms of efficacy and B cell-depleting agents and natalizumab toward the high side.
 

Why go low?

Why put someone on a low-efficacy drug? One reason is because they’re the safest options, he said, while the two highest-efficacy drugs – cladribine and alemtuzumab – are the least safe. But even the older, safer drugs can cause problems: Beta interferons can cause flu-like symptoms early on along with depression and miscarriage, and glatiramer acetate can spur injection site reactions and acute post injection syndrome “that can feel like a panic attack or even a heart attack.”

Dimethyl fumarate “is probably the easiest of the oral agents to initiate because there’s no extra doctor’s appointments. And there’s no concerns really about hair loss, liver failure, or birth defects,” he said. “But it’s one of the oral agents that has the most side effects associated with it.” Flushing is almost universal but “rarely a cause of discontinuation,” while gastrointestinal symptoms can lead to discontinuation.

Alemtuzumab, a high-efficacy drug that’s administered in two annual cycles, he said, is especially convenient but monthly labs are required for years to check for problems due to its dampening of the immune system. Patients on ocrelizumab must be closely monitored for the same reason.

There are other factors to consider. Lower-efficacy drugs tend to be better options in younger patients – “they’re more resilient, and they tend to recover a little bit better after their early relapses,” Dr. Rinker said.

The drugs are especially helpful in patients who recover well after their initial episodes and who have sensory instead of motor symptoms, he said.
 

The case for high efficacy

Higher-efficacy drugs are best for older patients and those with heavy disease burden.

What about the 40-year-old patient? She’s female (women get less sick from MS) and has low disease burden, suggesting that a lower-efficacy drug may be appropriate, he said. “On the other hand, she has an incomplete recovery, and she’s got spinal cord disease and motor symptoms, so the tendency is going to be more towards the higher-efficacy end of the [drug] spectrum.”

But which drug? S1P modulators aren’t a good option since they require redosing or titration if doses are missed: “It’s important that you don’t prescribe them to patients where you have concerns about compliance.”

Also, he said, “we don’t think we’re to the point that we’re willing to put her at risk of severe medical complications by putting her on medicines with a high monitoring burden like cladribine or alemtuzumab.”

The best option may be teriflunomide, a once-daily pill, he said. It’s forgiving if a patient misses a dose since the medication stays in the body for a long time.

“There’s no single right answer,” Dr. Rinker said. “But there are ways to eliminate a lot of the choices based upon what we know about the medications and what we know about the patient. Then we can tailor a specific range of medications for a specific patient.”

Dr. Rinker disclosed research support from GW Pharmaceuticals.

NATIONAL HARBOR, MD. – Treatment guidelines are helpful in treating relapsing-remitting multiple sclerosis (RRMS), a neurologist told colleagues, but they’re only useful to an extent. Consider his 40-year-old female patient who’s averse to vaccines, often misses appointments, and seems to be unable to take blood pressure drugs as prescribed. In this case, the best strategy may not be the drug with the highest efficacy.

“There’s no pharmaceutical insert that’s going to tell you what to do with all of this information,” John R. Rinker II, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s important to not only know about the disease and the specifics of the pharmaceuticals, but also about the patient’s personal circumstances, their comorbidities, their social situation, and how it all ties together.”

Fortunately, he said, there are about two dozen medication options now available for RRMS. Noting that his scale is at best “a crude approximation of reality,” he said their efficacy runs the gamut from low (glatiramer acetate and beta-interferons) to high (cladribine, alemtuzumab). He places sphingosine-1 phosphate (SIP1) modulators in the mid-range in terms of efficacy and B cell-depleting agents and natalizumab toward the high side.
 

Why go low?

Why put someone on a low-efficacy drug? One reason is because they’re the safest options, he said, while the two highest-efficacy drugs – cladribine and alemtuzumab – are the least safe. But even the older, safer drugs can cause problems: Beta interferons can cause flu-like symptoms early on along with depression and miscarriage, and glatiramer acetate can spur injection site reactions and acute post injection syndrome “that can feel like a panic attack or even a heart attack.”

Dimethyl fumarate “is probably the easiest of the oral agents to initiate because there’s no extra doctor’s appointments. And there’s no concerns really about hair loss, liver failure, or birth defects,” he said. “But it’s one of the oral agents that has the most side effects associated with it.” Flushing is almost universal but “rarely a cause of discontinuation,” while gastrointestinal symptoms can lead to discontinuation.

Alemtuzumab, a high-efficacy drug that’s administered in two annual cycles, he said, is especially convenient but monthly labs are required for years to check for problems due to its dampening of the immune system. Patients on ocrelizumab must be closely monitored for the same reason.

There are other factors to consider. Lower-efficacy drugs tend to be better options in younger patients – “they’re more resilient, and they tend to recover a little bit better after their early relapses,” Dr. Rinker said.

The drugs are especially helpful in patients who recover well after their initial episodes and who have sensory instead of motor symptoms, he said.
 

The case for high efficacy

Higher-efficacy drugs are best for older patients and those with heavy disease burden.

What about the 40-year-old patient? She’s female (women get less sick from MS) and has low disease burden, suggesting that a lower-efficacy drug may be appropriate, he said. “On the other hand, she has an incomplete recovery, and she’s got spinal cord disease and motor symptoms, so the tendency is going to be more towards the higher-efficacy end of the [drug] spectrum.”

But which drug? S1P modulators aren’t a good option since they require redosing or titration if doses are missed: “It’s important that you don’t prescribe them to patients where you have concerns about compliance.”

Also, he said, “we don’t think we’re to the point that we’re willing to put her at risk of severe medical complications by putting her on medicines with a high monitoring burden like cladribine or alemtuzumab.”

The best option may be teriflunomide, a once-daily pill, he said. It’s forgiving if a patient misses a dose since the medication stays in the body for a long time.

“There’s no single right answer,” Dr. Rinker said. “But there are ways to eliminate a lot of the choices based upon what we know about the medications and what we know about the patient. Then we can tailor a specific range of medications for a specific patient.”

Dr. Rinker disclosed research support from GW Pharmaceuticals.

NATIONAL HARBOR, MD. – Treatment guidelines are helpful in treating relapsing-remitting multiple sclerosis (RRMS), a neurologist told colleagues, but they’re only useful to an extent. Consider his 40-year-old female patient who’s averse to vaccines, often misses appointments, and seems to be unable to take blood pressure drugs as prescribed. In this case, the best strategy may not be the drug with the highest efficacy.

“There’s no pharmaceutical insert that’s going to tell you what to do with all of this information,” John R. Rinker II, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s important to not only know about the disease and the specifics of the pharmaceuticals, but also about the patient’s personal circumstances, their comorbidities, their social situation, and how it all ties together.”

Fortunately, he said, there are about two dozen medication options now available for RRMS. Noting that his scale is at best “a crude approximation of reality,” he said their efficacy runs the gamut from low (glatiramer acetate and beta-interferons) to high (cladribine, alemtuzumab). He places sphingosine-1 phosphate (SIP1) modulators in the mid-range in terms of efficacy and B cell-depleting agents and natalizumab toward the high side.
 

Why go low?

Why put someone on a low-efficacy drug? One reason is because they’re the safest options, he said, while the two highest-efficacy drugs – cladribine and alemtuzumab – are the least safe. But even the older, safer drugs can cause problems: Beta interferons can cause flu-like symptoms early on along with depression and miscarriage, and glatiramer acetate can spur injection site reactions and acute post injection syndrome “that can feel like a panic attack or even a heart attack.”

Dimethyl fumarate “is probably the easiest of the oral agents to initiate because there’s no extra doctor’s appointments. And there’s no concerns really about hair loss, liver failure, or birth defects,” he said. “But it’s one of the oral agents that has the most side effects associated with it.” Flushing is almost universal but “rarely a cause of discontinuation,” while gastrointestinal symptoms can lead to discontinuation.

Alemtuzumab, a high-efficacy drug that’s administered in two annual cycles, he said, is especially convenient but monthly labs are required for years to check for problems due to its dampening of the immune system. Patients on ocrelizumab must be closely monitored for the same reason.

There are other factors to consider. Lower-efficacy drugs tend to be better options in younger patients – “they’re more resilient, and they tend to recover a little bit better after their early relapses,” Dr. Rinker said.

The drugs are especially helpful in patients who recover well after their initial episodes and who have sensory instead of motor symptoms, he said.
 

The case for high efficacy

Higher-efficacy drugs are best for older patients and those with heavy disease burden.

What about the 40-year-old patient? She’s female (women get less sick from MS) and has low disease burden, suggesting that a lower-efficacy drug may be appropriate, he said. “On the other hand, she has an incomplete recovery, and she’s got spinal cord disease and motor symptoms, so the tendency is going to be more towards the higher-efficacy end of the [drug] spectrum.”

But which drug? S1P modulators aren’t a good option since they require redosing or titration if doses are missed: “It’s important that you don’t prescribe them to patients where you have concerns about compliance.”

Also, he said, “we don’t think we’re to the point that we’re willing to put her at risk of severe medical complications by putting her on medicines with a high monitoring burden like cladribine or alemtuzumab.”

The best option may be teriflunomide, a once-daily pill, he said. It’s forgiving if a patient misses a dose since the medication stays in the body for a long time.

“There’s no single right answer,” Dr. Rinker said. “But there are ways to eliminate a lot of the choices based upon what we know about the medications and what we know about the patient. Then we can tailor a specific range of medications for a specific patient.”

Dr. Rinker disclosed research support from GW Pharmaceuticals.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

Joining Gastroenterology as an editorial fellow is an invaluable experience for the future scientific career. When I joined the fellowship, my main objectives were to learn important aspects about scientific publishing, while improving my editorial and writing skills. Importantly, participating in the fellowship would allow me to determine fields in gastroenterology and hepatology that need more intensive research, evaluate and review manuscripts submitted to a high-impact journal, learn which aspects are important for manuscripts to be considered for publication, and learn how to prepare concise summaries to share with readers. As an editorial fellow, I would not only work with experts on manuscript review and editing, but also be mentored by experts in the field to prepare for a career in scientific publishing.

The application process is easy and straightforward. A curriculum vitae, motivation letter, and conflict of interest form are needed to be considered for the position. Furthermore, a letter of recommendation has to be provided from senior faculty. For the latter, it is beneficial to have worked with someone who is currently active in scientific publishing.

After joining the editorial board, fellows are assigned to associate editors based on their previous experience. Fellows are expected to peer-review manuscripts and discuss their reviews with the associate editors during a brief call or by email, where it is also determined whether additional feedback from the board of editors is needed to move manuscripts forward. If so, fellows are given the opportunity to present manuscripts they reviewed to the editorial board and prepare the decision letter with comments to the authors and editors. This experience teaches which qualities manuscripts need to fulfill to be considered for publication, and how to communicate decisions to authors. During the meetings with the editorial board, fellows are also encouraged to provide feedback for additional manuscripts discussed.

Additionally, fellows have the chance to work on the “Covering the Cover” section of the journal under close mentorship of the responsible editors. Here, they learn to draft short synopses of submitted manuscripts that should be highlighted in the respective sections to give readers a brief overview of important pieces of research with potential clinical applicability. This experience teaches how to write concisely and rephrase the main message of manuscripts without overstating findings and conclusions. Additionally, fellows are invited to write commentaries on recent articles published in other journals and highlight these to Gastroenterology’s readership. This experience teaches how to critically comment on published literature and point out its strengths and limitations. Overall, these learning experiences improve not only editorial and writing skills, but also knowledge in the respective areas of research.

Finally, fellows have the opportunity to write a commentary about a topic of their choice. This experience allows fellows to deepen their expertise in an area of research on an emerging topic they would like to highlight to their readers. Since this type of article is peer reviewed, reviewers’ comments help identify weaknesses of the initially submitted manuscript and increase the awareness about factors that need to be addressed to finally provide a high-quality article that is of value to Gastroenterology’s readership.

Concluding, being an editorial fellow for Gastroenterology is an extremely valuable experience. From an editorial aspect, fellows learn to review, summarize, and comment on submitted manuscripts, as well as which factors need to be addressed by manuscripts to be considered for publication to a high-impact journal. Additionally, fellows network with leaders in the field and expand their knowledge on topics they had not worked on previously. Overall, the fellowship helps improve editorial and writing skills, while staying current in the literature, a skill set that can be applied broadly in the future medical and scientific career.

Dr. Kefalakes is a clinical fellow and research group leader in the department of gastroenterology, hepatology, and endocrinology at Hannover (Germany) Medical School. She has nothing to declare.

Joining Gastroenterology as an editorial fellow is an invaluable experience for the future scientific career. When I joined the fellowship, my main objectives were to learn important aspects about scientific publishing, while improving my editorial and writing skills. Importantly, participating in the fellowship would allow me to determine fields in gastroenterology and hepatology that need more intensive research, evaluate and review manuscripts submitted to a high-impact journal, learn which aspects are important for manuscripts to be considered for publication, and learn how to prepare concise summaries to share with readers. As an editorial fellow, I would not only work with experts on manuscript review and editing, but also be mentored by experts in the field to prepare for a career in scientific publishing.

The application process is easy and straightforward. A curriculum vitae, motivation letter, and conflict of interest form are needed to be considered for the position. Furthermore, a letter of recommendation has to be provided from senior faculty. For the latter, it is beneficial to have worked with someone who is currently active in scientific publishing.

After joining the editorial board, fellows are assigned to associate editors based on their previous experience. Fellows are expected to peer-review manuscripts and discuss their reviews with the associate editors during a brief call or by email, where it is also determined whether additional feedback from the board of editors is needed to move manuscripts forward. If so, fellows are given the opportunity to present manuscripts they reviewed to the editorial board and prepare the decision letter with comments to the authors and editors. This experience teaches which qualities manuscripts need to fulfill to be considered for publication, and how to communicate decisions to authors. During the meetings with the editorial board, fellows are also encouraged to provide feedback for additional manuscripts discussed.

Additionally, fellows have the chance to work on the “Covering the Cover” section of the journal under close mentorship of the responsible editors. Here, they learn to draft short synopses of submitted manuscripts that should be highlighted in the respective sections to give readers a brief overview of important pieces of research with potential clinical applicability. This experience teaches how to write concisely and rephrase the main message of manuscripts without overstating findings and conclusions. Additionally, fellows are invited to write commentaries on recent articles published in other journals and highlight these to Gastroenterology’s readership. This experience teaches how to critically comment on published literature and point out its strengths and limitations. Overall, these learning experiences improve not only editorial and writing skills, but also knowledge in the respective areas of research.

Finally, fellows have the opportunity to write a commentary about a topic of their choice. This experience allows fellows to deepen their expertise in an area of research on an emerging topic they would like to highlight to their readers. Since this type of article is peer reviewed, reviewers’ comments help identify weaknesses of the initially submitted manuscript and increase the awareness about factors that need to be addressed to finally provide a high-quality article that is of value to Gastroenterology’s readership.

Concluding, being an editorial fellow for Gastroenterology is an extremely valuable experience. From an editorial aspect, fellows learn to review, summarize, and comment on submitted manuscripts, as well as which factors need to be addressed by manuscripts to be considered for publication to a high-impact journal. Additionally, fellows network with leaders in the field and expand their knowledge on topics they had not worked on previously. Overall, the fellowship helps improve editorial and writing skills, while staying current in the literature, a skill set that can be applied broadly in the future medical and scientific career.

Dr. Kefalakes is a clinical fellow and research group leader in the department of gastroenterology, hepatology, and endocrinology at Hannover (Germany) Medical School. She has nothing to declare.

Joining Gastroenterology as an editorial fellow is an invaluable experience for the future scientific career. When I joined the fellowship, my main objectives were to learn important aspects about scientific publishing, while improving my editorial and writing skills. Importantly, participating in the fellowship would allow me to determine fields in gastroenterology and hepatology that need more intensive research, evaluate and review manuscripts submitted to a high-impact journal, learn which aspects are important for manuscripts to be considered for publication, and learn how to prepare concise summaries to share with readers. As an editorial fellow, I would not only work with experts on manuscript review and editing, but also be mentored by experts in the field to prepare for a career in scientific publishing.

The application process is easy and straightforward. A curriculum vitae, motivation letter, and conflict of interest form are needed to be considered for the position. Furthermore, a letter of recommendation has to be provided from senior faculty. For the latter, it is beneficial to have worked with someone who is currently active in scientific publishing.

After joining the editorial board, fellows are assigned to associate editors based on their previous experience. Fellows are expected to peer-review manuscripts and discuss their reviews with the associate editors during a brief call or by email, where it is also determined whether additional feedback from the board of editors is needed to move manuscripts forward. If so, fellows are given the opportunity to present manuscripts they reviewed to the editorial board and prepare the decision letter with comments to the authors and editors. This experience teaches which qualities manuscripts need to fulfill to be considered for publication, and how to communicate decisions to authors. During the meetings with the editorial board, fellows are also encouraged to provide feedback for additional manuscripts discussed.

Additionally, fellows have the chance to work on the “Covering the Cover” section of the journal under close mentorship of the responsible editors. Here, they learn to draft short synopses of submitted manuscripts that should be highlighted in the respective sections to give readers a brief overview of important pieces of research with potential clinical applicability. This experience teaches how to write concisely and rephrase the main message of manuscripts without overstating findings and conclusions. Additionally, fellows are invited to write commentaries on recent articles published in other journals and highlight these to Gastroenterology’s readership. This experience teaches how to critically comment on published literature and point out its strengths and limitations. Overall, these learning experiences improve not only editorial and writing skills, but also knowledge in the respective areas of research.

Finally, fellows have the opportunity to write a commentary about a topic of their choice. This experience allows fellows to deepen their expertise in an area of research on an emerging topic they would like to highlight to their readers. Since this type of article is peer reviewed, reviewers’ comments help identify weaknesses of the initially submitted manuscript and increase the awareness about factors that need to be addressed to finally provide a high-quality article that is of value to Gastroenterology’s readership.

Concluding, being an editorial fellow for Gastroenterology is an extremely valuable experience. From an editorial aspect, fellows learn to review, summarize, and comment on submitted manuscripts, as well as which factors need to be addressed by manuscripts to be considered for publication to a high-impact journal. Additionally, fellows network with leaders in the field and expand their knowledge on topics they had not worked on previously. Overall, the fellowship helps improve editorial and writing skills, while staying current in the literature, a skill set that can be applied broadly in the future medical and scientific career.

Dr. Kefalakes is a clinical fellow and research group leader in the department of gastroenterology, hepatology, and endocrinology at Hannover (Germany) Medical School. She has nothing to declare.

Herpes zoster does not appear to increase dementia risk – on the contrary, the viral infection may offer some protection, a large population-based study suggests.

“We were surprised by these results [and] the reasons for the decreased risk are unclear,” study author Sigrun Alba Johannesdottir Schmidt, MD, PhD, with Aarhus (Denmark) University Hospital, said in a news release.

The study was published online in Neurology.
 

Conflicting findings

Herpes zoster (HZ) is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV). Previous population-based studies have reported both decreased and increased risks of dementia after having HZ.

It’s thought that HZ may contribute to the development of dementia through neuroinflammation, cerebral vasculopathy, or direct neural damage, but epidemiologic evidence is limited.

To investigate further, Dr. Schmidt and colleagues used Danish medical registries to identify 247,305 people who had visited a hospital for HZ or were prescribed antiviral medication for HZ over a 20-year period and matched them to 1,235,890 people who did not have HZ. For both cohorts, the median age was 64 years, and 61% were women.

Dementia was diagnosed in 9.7% of zoster patients and 10.3% of matched control persons during up to 21 years of follow-up.

Contrary to the researchers’ expectation, HZ was associated with a small (7%) decreased relative risk of all-cause dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.90-0.95).

There was no increased long-term risk of dementia in subgroup analyses, except possibly among those with HZ that involved the central nervous system (HR, 1.94; 95% CI, 0.78-4.80), which has been shown before.

However, the population attributable fraction of dementia caused by this rare complication is low (< 1%), suggesting that universal vaccination against VZV in the elderly has limited potential to reduce dementia risk, the investigators noted.

Nonetheless, Dr. Schmidt said shingles vaccination should be encouraged in older people because it can prevent complications from the disease.

The research team admitted that the slightly decreased long-term risk of dementia, including Alzheimer’s disease, was “unexpected.” The reasons for this decreased risk are unclear, they say, and could be explained by missed diagnoses of shingles in people with undiagnosed dementia.

They were not able to examine whether antiviral treatment modifies the association between HZ and dementia and said that this topic merits further research.

The study was supported by the Edel and Wilhelm Daubenmerkls Charitable Foundation. The authors disclosed no relevant financial relationships.

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

Herpes zoster does not appear to increase dementia risk – on the contrary, the viral infection may offer some protection, a large population-based study suggests.

“We were surprised by these results [and] the reasons for the decreased risk are unclear,” study author Sigrun Alba Johannesdottir Schmidt, MD, PhD, with Aarhus (Denmark) University Hospital, said in a news release.

The study was published online in Neurology.
 

Conflicting findings

Herpes zoster (HZ) is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV). Previous population-based studies have reported both decreased and increased risks of dementia after having HZ.

It’s thought that HZ may contribute to the development of dementia through neuroinflammation, cerebral vasculopathy, or direct neural damage, but epidemiologic evidence is limited.

To investigate further, Dr. Schmidt and colleagues used Danish medical registries to identify 247,305 people who had visited a hospital for HZ or were prescribed antiviral medication for HZ over a 20-year period and matched them to 1,235,890 people who did not have HZ. For both cohorts, the median age was 64 years, and 61% were women.

Dementia was diagnosed in 9.7% of zoster patients and 10.3% of matched control persons during up to 21 years of follow-up.

Contrary to the researchers’ expectation, HZ was associated with a small (7%) decreased relative risk of all-cause dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.90-0.95).

There was no increased long-term risk of dementia in subgroup analyses, except possibly among those with HZ that involved the central nervous system (HR, 1.94; 95% CI, 0.78-4.80), which has been shown before.

However, the population attributable fraction of dementia caused by this rare complication is low (< 1%), suggesting that universal vaccination against VZV in the elderly has limited potential to reduce dementia risk, the investigators noted.

Nonetheless, Dr. Schmidt said shingles vaccination should be encouraged in older people because it can prevent complications from the disease.

The research team admitted that the slightly decreased long-term risk of dementia, including Alzheimer’s disease, was “unexpected.” The reasons for this decreased risk are unclear, they say, and could be explained by missed diagnoses of shingles in people with undiagnosed dementia.

They were not able to examine whether antiviral treatment modifies the association between HZ and dementia and said that this topic merits further research.

The study was supported by the Edel and Wilhelm Daubenmerkls Charitable Foundation. The authors disclosed no relevant financial relationships.

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

Herpes zoster does not appear to increase dementia risk – on the contrary, the viral infection may offer some protection, a large population-based study suggests.

“We were surprised by these results [and] the reasons for the decreased risk are unclear,” study author Sigrun Alba Johannesdottir Schmidt, MD, PhD, with Aarhus (Denmark) University Hospital, said in a news release.

The study was published online in Neurology.
 

Conflicting findings

Herpes zoster (HZ) is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV). Previous population-based studies have reported both decreased and increased risks of dementia after having HZ.

It’s thought that HZ may contribute to the development of dementia through neuroinflammation, cerebral vasculopathy, or direct neural damage, but epidemiologic evidence is limited.

To investigate further, Dr. Schmidt and colleagues used Danish medical registries to identify 247,305 people who had visited a hospital for HZ or were prescribed antiviral medication for HZ over a 20-year period and matched them to 1,235,890 people who did not have HZ. For both cohorts, the median age was 64 years, and 61% were women.

Dementia was diagnosed in 9.7% of zoster patients and 10.3% of matched control persons during up to 21 years of follow-up.

Contrary to the researchers’ expectation, HZ was associated with a small (7%) decreased relative risk of all-cause dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.90-0.95).

There was no increased long-term risk of dementia in subgroup analyses, except possibly among those with HZ that involved the central nervous system (HR, 1.94; 95% CI, 0.78-4.80), which has been shown before.

However, the population attributable fraction of dementia caused by this rare complication is low (< 1%), suggesting that universal vaccination against VZV in the elderly has limited potential to reduce dementia risk, the investigators noted.

Nonetheless, Dr. Schmidt said shingles vaccination should be encouraged in older people because it can prevent complications from the disease.

The research team admitted that the slightly decreased long-term risk of dementia, including Alzheimer’s disease, was “unexpected.” The reasons for this decreased risk are unclear, they say, and could be explained by missed diagnoses of shingles in people with undiagnosed dementia.

They were not able to examine whether antiviral treatment modifies the association between HZ and dementia and said that this topic merits further research.

The study was supported by the Edel and Wilhelm Daubenmerkls Charitable Foundation. The authors disclosed no relevant financial relationships.

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

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

An artificial intelligence (AI)–based computer-aided polyp detection (CADe) system missed fewer adenomas, polyps, and sessile serrated lesions and identified more adenomas per colonoscopy than a high-definition white light (HDWL) colonoscopy, according to findings from a randomized study.

While adenoma detection by colonoscopy is associated with a reduced risk of interval colon cancer, detection rates of adenomas vary among physicians. AI approaches, such as machine learning and deep learning, may improve adenoma detection rates during colonoscopy and thus potentially improve outcomes for patients, suggested study authors led by Jeremy R. Glissen Brown, MD, of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, who reported their trial findings in Clinical Gastroenterology and Hepatology.

The investigators explained that, although AI approaches may offer benefits in adenoma detection, there have been no prospective data for U.S. populations on the efficacy of an AI-based CADe system for improving adenoma detection rates (ADRs) and reducing adenoma miss rates (AMRs). To overcome this research gap, the investigators performed a prospective, multicenter, single-blind randomized tandem colonoscopy study which assessed a deep learning–based CADe system in 232 patients.

Individuals who presented to the four included U.S. medical centers for either colorectal cancer screening or surveillance were randomly assigned to the CADe system colonoscopy first (n = 116) or HDWL colonoscopy first (n = 116). This was immediately followed by the other procedure, in tandem fashion, performed by the same endoscopist. AMR was the primary outcome of interest, while secondary outcomes were adenomas per colonoscopy (APC) and the miss rate of sessile serrated lesions (SSL).

The researchers excluded 9 patients, which resulted in a total patient population of 223 patients. Approximately 45.3% of the cohort was female, 67.7% were White, and 21% were Black. Most patients (60%) were indicated for primary colorectal cancer screening.

Compared with the HDWL-first group, the AMR was significantly lower in the CADe-first group (31.25% vs. 20.12%, respectively; P = .0247). The researchers commented that, although the CADe system resulted in a statistically significantly lower AMR, the rate still reflects missed adenomas.

Additionally, the CADe-first group had a lower SSL miss rate, compared with the HDWL-first group (7.14% vs. 42.11%, respectively; P = .0482). The researchers noted that their study is one of the first research studies to show that a computer-assisted polyp detection system can reduce the SSL miss rate. The first-pass APC was also significantly higher in the CADe-first group (1.19 vs. 0.90; P = .0323). No statistically significant difference was observed between the groups in regard to the first-pass ADR (50.44% for the CADe-first group vs. 43.64 % for the HDWL-first group; P = .3091).

A multivariate logistic regression analysis identified three significant factors predictive of missed polyps: use of HDWL first vs. the computer-assisted detection system first (odds ratio, 1.8830; P = .0214), age 65 years or younger (OR, 1.7390; P = .0451), and right colon vs. other location (OR, 1.7865; P = .0436).

According to the researchers, the study was not powered to identify differences in ADR, thereby limiting the interpretation of this analysis. In addition, the investigators noted that the tandem colonoscopy study design is limited in its generalizability to real-world clinical settings. Also, given that endoscopists were not blinded to group assignments while performing each withdrawal, the researchers commented that “it is possible that endoscopist performance was influenced by being observed or that endoscopists who participated for the length of the study became over-reliant on” the CADe system during withdrawal, resulting in an underestimate or overestimation of the system’s performance.

The authors concluded that their findings suggest that an AI-based CADe system with colonoscopy “has the potential to decrease interprovider variability in colonoscopy quality by reducing AMR, even in experienced providers.”

This was an investigator-initiated study, with research software and study funding provided by Wision AI. The investigators reported relationships with Wision AI, as well as Olympus, Fujifilm, and Medtronic.

An artificial intelligence (AI)–based computer-aided polyp detection (CADe) system missed fewer adenomas, polyps, and sessile serrated lesions and identified more adenomas per colonoscopy than a high-definition white light (HDWL) colonoscopy, according to findings from a randomized study.

While adenoma detection by colonoscopy is associated with a reduced risk of interval colon cancer, detection rates of adenomas vary among physicians. AI approaches, such as machine learning and deep learning, may improve adenoma detection rates during colonoscopy and thus potentially improve outcomes for patients, suggested study authors led by Jeremy R. Glissen Brown, MD, of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, who reported their trial findings in Clinical Gastroenterology and Hepatology.

The investigators explained that, although AI approaches may offer benefits in adenoma detection, there have been no prospective data for U.S. populations on the efficacy of an AI-based CADe system for improving adenoma detection rates (ADRs) and reducing adenoma miss rates (AMRs). To overcome this research gap, the investigators performed a prospective, multicenter, single-blind randomized tandem colonoscopy study which assessed a deep learning–based CADe system in 232 patients.

Individuals who presented to the four included U.S. medical centers for either colorectal cancer screening or surveillance were randomly assigned to the CADe system colonoscopy first (n = 116) or HDWL colonoscopy first (n = 116). This was immediately followed by the other procedure, in tandem fashion, performed by the same endoscopist. AMR was the primary outcome of interest, while secondary outcomes were adenomas per colonoscopy (APC) and the miss rate of sessile serrated lesions (SSL).

The researchers excluded 9 patients, which resulted in a total patient population of 223 patients. Approximately 45.3% of the cohort was female, 67.7% were White, and 21% were Black. Most patients (60%) were indicated for primary colorectal cancer screening.

Compared with the HDWL-first group, the AMR was significantly lower in the CADe-first group (31.25% vs. 20.12%, respectively; P = .0247). The researchers commented that, although the CADe system resulted in a statistically significantly lower AMR, the rate still reflects missed adenomas.

Additionally, the CADe-first group had a lower SSL miss rate, compared with the HDWL-first group (7.14% vs. 42.11%, respectively; P = .0482). The researchers noted that their study is one of the first research studies to show that a computer-assisted polyp detection system can reduce the SSL miss rate. The first-pass APC was also significantly higher in the CADe-first group (1.19 vs. 0.90; P = .0323). No statistically significant difference was observed between the groups in regard to the first-pass ADR (50.44% for the CADe-first group vs. 43.64 % for the HDWL-first group; P = .3091).

A multivariate logistic regression analysis identified three significant factors predictive of missed polyps: use of HDWL first vs. the computer-assisted detection system first (odds ratio, 1.8830; P = .0214), age 65 years or younger (OR, 1.7390; P = .0451), and right colon vs. other location (OR, 1.7865; P = .0436).

According to the researchers, the study was not powered to identify differences in ADR, thereby limiting the interpretation of this analysis. In addition, the investigators noted that the tandem colonoscopy study design is limited in its generalizability to real-world clinical settings. Also, given that endoscopists were not blinded to group assignments while performing each withdrawal, the researchers commented that “it is possible that endoscopist performance was influenced by being observed or that endoscopists who participated for the length of the study became over-reliant on” the CADe system during withdrawal, resulting in an underestimate or overestimation of the system’s performance.

The authors concluded that their findings suggest that an AI-based CADe system with colonoscopy “has the potential to decrease interprovider variability in colonoscopy quality by reducing AMR, even in experienced providers.”

This was an investigator-initiated study, with research software and study funding provided by Wision AI. The investigators reported relationships with Wision AI, as well as Olympus, Fujifilm, and Medtronic.

An artificial intelligence (AI)–based computer-aided polyp detection (CADe) system missed fewer adenomas, polyps, and sessile serrated lesions and identified more adenomas per colonoscopy than a high-definition white light (HDWL) colonoscopy, according to findings from a randomized study.

While adenoma detection by colonoscopy is associated with a reduced risk of interval colon cancer, detection rates of adenomas vary among physicians. AI approaches, such as machine learning and deep learning, may improve adenoma detection rates during colonoscopy and thus potentially improve outcomes for patients, suggested study authors led by Jeremy R. Glissen Brown, MD, of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, who reported their trial findings in Clinical Gastroenterology and Hepatology.

The investigators explained that, although AI approaches may offer benefits in adenoma detection, there have been no prospective data for U.S. populations on the efficacy of an AI-based CADe system for improving adenoma detection rates (ADRs) and reducing adenoma miss rates (AMRs). To overcome this research gap, the investigators performed a prospective, multicenter, single-blind randomized tandem colonoscopy study which assessed a deep learning–based CADe system in 232 patients.

Individuals who presented to the four included U.S. medical centers for either colorectal cancer screening or surveillance were randomly assigned to the CADe system colonoscopy first (n = 116) or HDWL colonoscopy first (n = 116). This was immediately followed by the other procedure, in tandem fashion, performed by the same endoscopist. AMR was the primary outcome of interest, while secondary outcomes were adenomas per colonoscopy (APC) and the miss rate of sessile serrated lesions (SSL).

The researchers excluded 9 patients, which resulted in a total patient population of 223 patients. Approximately 45.3% of the cohort was female, 67.7% were White, and 21% were Black. Most patients (60%) were indicated for primary colorectal cancer screening.

Compared with the HDWL-first group, the AMR was significantly lower in the CADe-first group (31.25% vs. 20.12%, respectively; P = .0247). The researchers commented that, although the CADe system resulted in a statistically significantly lower AMR, the rate still reflects missed adenomas.

Additionally, the CADe-first group had a lower SSL miss rate, compared with the HDWL-first group (7.14% vs. 42.11%, respectively; P = .0482). The researchers noted that their study is one of the first research studies to show that a computer-assisted polyp detection system can reduce the SSL miss rate. The first-pass APC was also significantly higher in the CADe-first group (1.19 vs. 0.90; P = .0323). No statistically significant difference was observed between the groups in regard to the first-pass ADR (50.44% for the CADe-first group vs. 43.64 % for the HDWL-first group; P = .3091).

A multivariate logistic regression analysis identified three significant factors predictive of missed polyps: use of HDWL first vs. the computer-assisted detection system first (odds ratio, 1.8830; P = .0214), age 65 years or younger (OR, 1.7390; P = .0451), and right colon vs. other location (OR, 1.7865; P = .0436).

According to the researchers, the study was not powered to identify differences in ADR, thereby limiting the interpretation of this analysis. In addition, the investigators noted that the tandem colonoscopy study design is limited in its generalizability to real-world clinical settings. Also, given that endoscopists were not blinded to group assignments while performing each withdrawal, the researchers commented that “it is possible that endoscopist performance was influenced by being observed or that endoscopists who participated for the length of the study became over-reliant on” the CADe system during withdrawal, resulting in an underestimate or overestimation of the system’s performance.

The authors concluded that their findings suggest that an AI-based CADe system with colonoscopy “has the potential to decrease interprovider variability in colonoscopy quality by reducing AMR, even in experienced providers.”

This was an investigator-initiated study, with research software and study funding provided by Wision AI. The investigators reported relationships with Wision AI, as well as Olympus, Fujifilm, and Medtronic.

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

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

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

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

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

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