MDedge Endocrinology

A new group of nonhormonal drugs currently in clinical trials shows strong promise for treating menopausal hot flashes as effectively as hormones, researchers told attendees at the virtual North American Menopause Society 2020 Annual Meeting.

“The KNDy [kisspeptin/neurokinin B/dynorphin] neuron manipulation is really exciting and holds great promise for rapid and highly effective amelioration of hot flashes, up to 80%, and improvement in other menopausal symptoms, though we’re still looking at the safety in phase 3 trials,” reported Susan D. Reed, MD, MPH, director of the Women’s Reproductive Health Research Program at the University of Washington, Seattle.

“If we continue to see good safety data, these are going to be the greatest things since sliced bread,” Dr. Reed said in an interview. “I don’t think we’ve seen anything like this in menopause therapeutics in a long time.”

While several nonhormonal drugs are already used to treat vasomotor symptoms in menopausal women with and without breast cancer, none are as effective as hormone treatments.

“For now, the SSRIs, SNRIs [serotonin norepinephrine reuptake inhibitors], and GABAergics are the best frontline nonhormonal options with a moderate effect, and clonidine and oxybutynin are effective, but we see more side effects with these,” Dr. Reed said. She noted the importance of considering patients’ mood, sleep, pain, sexual function, weight gain, overactive bladder, blood pressure, and individual quality of life (QOL) goals in tailoring those therapies.

But women still need more nonhormonal options that are at least as effective as hormonal options, Dr. Reed said. Some women are unable to take hormonal options because they are at risk for blood clots or breast cancer.

“Then there’s preference,” she said. “Sometimes people don’t like the way they feel when they take hormones, or they just don’t want hormones in their body. It’s absolutely critical to have these options available for women.”

Nanette F. Santoro, MD, a professor of ob.gyn. at the University of Colorado at Denver, Aurora, who was not involved in the presentation, said in an interview that physicians may not always realize the extent to which vasomotor symptoms interfere with women’s daily lives.

“They have an eroding effect on QOL that is not appreciated sometimes,” she said. Though hot flashes eventually subside in most women, others may continue to experience them into their 70s, when hormonal therapies can begin causing more harm than benefit.

“It goes underappreciated that, for a proportion of women, hot flashes will never go away, and they’re just as bad [as] when they were in their 50s,” Dr. Santoro said. “They need to be treated, and the nonhormonal treatments do not work for everybody.”
 

Promising KNDy therapeutics

Autopsy studies of postmenopausal women revealed that a complex of neurons in the hypothalamus was “massively hypertrophied” and sits right next to the thermoregulatory center of the brain, Dr. Reed explained.

The complex produces three types of molecules: kisspeptin (a neuropeptide), neurokinin B (a neuropeptide), and dynorphin (a kappa opioid), collectively referred to as the KNDy. The KNDy neural complex is located in the same place as the majority of hormone receptors in the arcuate nucleus, a collection of nerve cells in the hypothalamus.

The current hypothesis is that the KNDy neurons, which communicate with each other, become hyperactivated and cause hot flashes by spilling over to and triggering the thermoregulatory center next door. NKB (kisspeptin and neurokinin B) agonists activate KNDy neurons and dynorphin agonists inactivate KNDy, so the expectation is that NKB antagonists or dynorphin agonists would stop hot flashes.

Indeed, research published in 2015 showed that women taking kappa agonists experienced fewer hot flashes than women in the placebo group. However, no peripherally restricted kappa agonists are currently in clinical trials, so their future as therapeutics is unclear.

Right now, three different NK antagonists are in the pipeline for reducing vasomotor symptoms: MLE 4901 (pavinetant) and ESN364 (fezolinetant) are both NK3R antagonists, and NT-814 is a dual NK1R/NK3R antagonist. All three of these drugs were originally developed to treat schizophrenia.

Phase 2 clinical trials of pavinetant were discontinued in November 2017 by Millendo Therapeutics because 3 of 28 women experienced abnormal liver function, which normalized within 90 days. However, the study had shown an 80% decrease in hot flashes in women taking pavinetant, compared with a 30% decrease in the placebo group.

Fezolinetant, currently in phase 3 trials with Astellas, showed a dose response effect on reproductive hormones in phase 1 studies and a short half-life (4-6 hours) in women. It also showed no concerning side effects.

“There was, in fact, a decrease in the endometrial thickness, a delayed or impeded ovulation and a prolonged cycle duration,” Reed said.

The subsequent phase 2a study showed a reduction of five hot flashes a day (93% decrease), compared with placebo (54% decrease, P <.001) “with an abrupt return to baseline hot flash frequency after cessation,” she said. Improvements also occurred in sleep quality, quality of life, disability, and interference of hot flashes in daily life.

The phase 2b study found no difference in effects between once-daily versus twice-daily doses. However, two severe adverse events occurred: a drug-induced liver injury in one woman and cholelithiasis in another, both on the 60-mg, once-daily dose. Additionally, five women on varying doses had transient increases (above 1000 U/L) in creatinine kinase, though apparently without dose response.

A 52-week, three-arm, phase 3 trial of fezolinetant is currently under way with a goal of enrolling 1,740 participants, and plans to be completed by December 2021. Participants will undergo regular adverse event screening first biweekly, then monthly, with vital signs, blood, and urine monitoring.

Meanwhile, NT-814 from KaNDy Therapeutics, has completed phase 2a and phase 2b trials with phase 3 slated to begin in 2021. Adverse events in phase 1 included sleepiness and headache, and it had a long half-life (about 26 hours) and rapid absorption (an hour).

The phase 2a trial found a reduction of five hot flashes a day, compared with placebo, with main side effects again being sleepiness and headache. No events of abnormal liver function occurred. Phase 2b results have not been published.

So far, existing research suggests that KNDy interventions will involve a single daily oral dose that begins taking effect within 3 days and is fully in effect within 1-2 weeks. The reduction in hot flashes, about five fewer a day, is more effective than any other currently used nonhormonal medications for vasomotor symptoms. SSRIs and SNRIs tend to result in 1.5-2 fewer hot flashes a day, and gabapentin results in about 3 fewer per day. It will take longer-term studies, however, and paying attention to liver concerns for the NK3R antagonists to move into clinic.

“We want to keep our eye on the [luteinizing hormone] because if it decreases too much, it could adversely affect sexual function, and this does appear to be a dose-response finding,” Dr. Reed said. It would also be ideal, she said, to target only the KNDy neurons with NK3 antagonists without effects on the NK3 receptors in the liver.
 

Other nonhormonal options

Oxybutynin is another a nonhormonal agent under investigation for vasomotor symptoms. It’s an anticholinergic that resulted in 80% fewer hot flashes, compared with 30% with placebo in a 2016 trial, but 52% of women complained of dry mouth. A more recent study similarly found high efficacy – a 60%-80% drop in hot flashes, compared with 30% with placebo – but also side effects of dry mouth, difficulty urinating, and abdominal pain.

Finally, Dr. Reed mentioned three other agents under investigation as possible nonhormonal therapeutics, though she has little information about them. They include MT-8554 by Mitsubishi Tanabe; FP-101 by Fervent Pharmaceuticals; and Q-122 by QUE Oncology with Emory University, Atlanta, and the University of Queensland, Brisbane, Australia. 

None of the currently available nonhormonal options provide as high efficacy as hormones, but they do reduce symptoms:

Clonidine is an off-label option some physicians already use as a nonhormonal treatment for vasomotor symptoms, but again, the side effects are problematic: dry mouth, constipation, drowsiness, postural hypotension, and poor sleep.

Paroxetine, at 7.5-10 mg, is the only FDA-approved nonhormonal treatment for vasomotor symptoms, but she listed other off-label options found effective in evidence reviews: gabapentin (100-2,400 mg), venlafaxine (37.5-75 mg), citalopram (10 mg), desvenlafaxine (150 mg), and escitalopram (10 mg).

“I want you to take note of the lower doses in all of these products that are efficacious above those doses that might be used for mood,” Dr. Reed added.

Dr. Reed receives royalties from UpToDate and research funding from Bayer. Dr. Santoro owns stock in MenoGeniX and serves as a consultant or advisor to Ansh Labs, MenoGeniX, and Ogeda/Astellas.

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

A new group of nonhormonal drugs currently in clinical trials shows strong promise for treating menopausal hot flashes as effectively as hormones, researchers told attendees at the virtual North American Menopause Society 2020 Annual Meeting.

“The KNDy [kisspeptin/neurokinin B/dynorphin] neuron manipulation is really exciting and holds great promise for rapid and highly effective amelioration of hot flashes, up to 80%, and improvement in other menopausal symptoms, though we’re still looking at the safety in phase 3 trials,” reported Susan D. Reed, MD, MPH, director of the Women’s Reproductive Health Research Program at the University of Washington, Seattle.

“If we continue to see good safety data, these are going to be the greatest things since sliced bread,” Dr. Reed said in an interview. “I don’t think we’ve seen anything like this in menopause therapeutics in a long time.”

While several nonhormonal drugs are already used to treat vasomotor symptoms in menopausal women with and without breast cancer, none are as effective as hormone treatments.

“For now, the SSRIs, SNRIs [serotonin norepinephrine reuptake inhibitors], and GABAergics are the best frontline nonhormonal options with a moderate effect, and clonidine and oxybutynin are effective, but we see more side effects with these,” Dr. Reed said. She noted the importance of considering patients’ mood, sleep, pain, sexual function, weight gain, overactive bladder, blood pressure, and individual quality of life (QOL) goals in tailoring those therapies.

But women still need more nonhormonal options that are at least as effective as hormonal options, Dr. Reed said. Some women are unable to take hormonal options because they are at risk for blood clots or breast cancer.

“Then there’s preference,” she said. “Sometimes people don’t like the way they feel when they take hormones, or they just don’t want hormones in their body. It’s absolutely critical to have these options available for women.”

Nanette F. Santoro, MD, a professor of ob.gyn. at the University of Colorado at Denver, Aurora, who was not involved in the presentation, said in an interview that physicians may not always realize the extent to which vasomotor symptoms interfere with women’s daily lives.

“They have an eroding effect on QOL that is not appreciated sometimes,” she said. Though hot flashes eventually subside in most women, others may continue to experience them into their 70s, when hormonal therapies can begin causing more harm than benefit.

“It goes underappreciated that, for a proportion of women, hot flashes will never go away, and they’re just as bad [as] when they were in their 50s,” Dr. Santoro said. “They need to be treated, and the nonhormonal treatments do not work for everybody.”
 

Promising KNDy therapeutics

Autopsy studies of postmenopausal women revealed that a complex of neurons in the hypothalamus was “massively hypertrophied” and sits right next to the thermoregulatory center of the brain, Dr. Reed explained.

The complex produces three types of molecules: kisspeptin (a neuropeptide), neurokinin B (a neuropeptide), and dynorphin (a kappa opioid), collectively referred to as the KNDy. The KNDy neural complex is located in the same place as the majority of hormone receptors in the arcuate nucleus, a collection of nerve cells in the hypothalamus.

The current hypothesis is that the KNDy neurons, which communicate with each other, become hyperactivated and cause hot flashes by spilling over to and triggering the thermoregulatory center next door. NKB (kisspeptin and neurokinin B) agonists activate KNDy neurons and dynorphin agonists inactivate KNDy, so the expectation is that NKB antagonists or dynorphin agonists would stop hot flashes.

Indeed, research published in 2015 showed that women taking kappa agonists experienced fewer hot flashes than women in the placebo group. However, no peripherally restricted kappa agonists are currently in clinical trials, so their future as therapeutics is unclear.

Right now, three different NK antagonists are in the pipeline for reducing vasomotor symptoms: MLE 4901 (pavinetant) and ESN364 (fezolinetant) are both NK3R antagonists, and NT-814 is a dual NK1R/NK3R antagonist. All three of these drugs were originally developed to treat schizophrenia.

Phase 2 clinical trials of pavinetant were discontinued in November 2017 by Millendo Therapeutics because 3 of 28 women experienced abnormal liver function, which normalized within 90 days. However, the study had shown an 80% decrease in hot flashes in women taking pavinetant, compared with a 30% decrease in the placebo group.

Fezolinetant, currently in phase 3 trials with Astellas, showed a dose response effect on reproductive hormones in phase 1 studies and a short half-life (4-6 hours) in women. It also showed no concerning side effects.

“There was, in fact, a decrease in the endometrial thickness, a delayed or impeded ovulation and a prolonged cycle duration,” Reed said.

The subsequent phase 2a study showed a reduction of five hot flashes a day (93% decrease), compared with placebo (54% decrease, P <.001) “with an abrupt return to baseline hot flash frequency after cessation,” she said. Improvements also occurred in sleep quality, quality of life, disability, and interference of hot flashes in daily life.

The phase 2b study found no difference in effects between once-daily versus twice-daily doses. However, two severe adverse events occurred: a drug-induced liver injury in one woman and cholelithiasis in another, both on the 60-mg, once-daily dose. Additionally, five women on varying doses had transient increases (above 1000 U/L) in creatinine kinase, though apparently without dose response.

A 52-week, three-arm, phase 3 trial of fezolinetant is currently under way with a goal of enrolling 1,740 participants, and plans to be completed by December 2021. Participants will undergo regular adverse event screening first biweekly, then monthly, with vital signs, blood, and urine monitoring.

Meanwhile, NT-814 from KaNDy Therapeutics, has completed phase 2a and phase 2b trials with phase 3 slated to begin in 2021. Adverse events in phase 1 included sleepiness and headache, and it had a long half-life (about 26 hours) and rapid absorption (an hour).

The phase 2a trial found a reduction of five hot flashes a day, compared with placebo, with main side effects again being sleepiness and headache. No events of abnormal liver function occurred. Phase 2b results have not been published.

So far, existing research suggests that KNDy interventions will involve a single daily oral dose that begins taking effect within 3 days and is fully in effect within 1-2 weeks. The reduction in hot flashes, about five fewer a day, is more effective than any other currently used nonhormonal medications for vasomotor symptoms. SSRIs and SNRIs tend to result in 1.5-2 fewer hot flashes a day, and gabapentin results in about 3 fewer per day. It will take longer-term studies, however, and paying attention to liver concerns for the NK3R antagonists to move into clinic.

“We want to keep our eye on the [luteinizing hormone] because if it decreases too much, it could adversely affect sexual function, and this does appear to be a dose-response finding,” Dr. Reed said. It would also be ideal, she said, to target only the KNDy neurons with NK3 antagonists without effects on the NK3 receptors in the liver.
 

Other nonhormonal options

Oxybutynin is another a nonhormonal agent under investigation for vasomotor symptoms. It’s an anticholinergic that resulted in 80% fewer hot flashes, compared with 30% with placebo in a 2016 trial, but 52% of women complained of dry mouth. A more recent study similarly found high efficacy – a 60%-80% drop in hot flashes, compared with 30% with placebo – but also side effects of dry mouth, difficulty urinating, and abdominal pain.

Finally, Dr. Reed mentioned three other agents under investigation as possible nonhormonal therapeutics, though she has little information about them. They include MT-8554 by Mitsubishi Tanabe; FP-101 by Fervent Pharmaceuticals; and Q-122 by QUE Oncology with Emory University, Atlanta, and the University of Queensland, Brisbane, Australia. 

None of the currently available nonhormonal options provide as high efficacy as hormones, but they do reduce symptoms:

Clonidine is an off-label option some physicians already use as a nonhormonal treatment for vasomotor symptoms, but again, the side effects are problematic: dry mouth, constipation, drowsiness, postural hypotension, and poor sleep.

Paroxetine, at 7.5-10 mg, is the only FDA-approved nonhormonal treatment for vasomotor symptoms, but she listed other off-label options found effective in evidence reviews: gabapentin (100-2,400 mg), venlafaxine (37.5-75 mg), citalopram (10 mg), desvenlafaxine (150 mg), and escitalopram (10 mg).

“I want you to take note of the lower doses in all of these products that are efficacious above those doses that might be used for mood,” Dr. Reed added.

Dr. Reed receives royalties from UpToDate and research funding from Bayer. Dr. Santoro owns stock in MenoGeniX and serves as a consultant or advisor to Ansh Labs, MenoGeniX, and Ogeda/Astellas.

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

A new group of nonhormonal drugs currently in clinical trials shows strong promise for treating menopausal hot flashes as effectively as hormones, researchers told attendees at the virtual North American Menopause Society 2020 Annual Meeting.

“The KNDy [kisspeptin/neurokinin B/dynorphin] neuron manipulation is really exciting and holds great promise for rapid and highly effective amelioration of hot flashes, up to 80%, and improvement in other menopausal symptoms, though we’re still looking at the safety in phase 3 trials,” reported Susan D. Reed, MD, MPH, director of the Women’s Reproductive Health Research Program at the University of Washington, Seattle.

“If we continue to see good safety data, these are going to be the greatest things since sliced bread,” Dr. Reed said in an interview. “I don’t think we’ve seen anything like this in menopause therapeutics in a long time.”

While several nonhormonal drugs are already used to treat vasomotor symptoms in menopausal women with and without breast cancer, none are as effective as hormone treatments.

“For now, the SSRIs, SNRIs [serotonin norepinephrine reuptake inhibitors], and GABAergics are the best frontline nonhormonal options with a moderate effect, and clonidine and oxybutynin are effective, but we see more side effects with these,” Dr. Reed said. She noted the importance of considering patients’ mood, sleep, pain, sexual function, weight gain, overactive bladder, blood pressure, and individual quality of life (QOL) goals in tailoring those therapies.

But women still need more nonhormonal options that are at least as effective as hormonal options, Dr. Reed said. Some women are unable to take hormonal options because they are at risk for blood clots or breast cancer.

“Then there’s preference,” she said. “Sometimes people don’t like the way they feel when they take hormones, or they just don’t want hormones in their body. It’s absolutely critical to have these options available for women.”

Nanette F. Santoro, MD, a professor of ob.gyn. at the University of Colorado at Denver, Aurora, who was not involved in the presentation, said in an interview that physicians may not always realize the extent to which vasomotor symptoms interfere with women’s daily lives.

“They have an eroding effect on QOL that is not appreciated sometimes,” she said. Though hot flashes eventually subside in most women, others may continue to experience them into their 70s, when hormonal therapies can begin causing more harm than benefit.

“It goes underappreciated that, for a proportion of women, hot flashes will never go away, and they’re just as bad [as] when they were in their 50s,” Dr. Santoro said. “They need to be treated, and the nonhormonal treatments do not work for everybody.”
 

Promising KNDy therapeutics

Autopsy studies of postmenopausal women revealed that a complex of neurons in the hypothalamus was “massively hypertrophied” and sits right next to the thermoregulatory center of the brain, Dr. Reed explained.

The complex produces three types of molecules: kisspeptin (a neuropeptide), neurokinin B (a neuropeptide), and dynorphin (a kappa opioid), collectively referred to as the KNDy. The KNDy neural complex is located in the same place as the majority of hormone receptors in the arcuate nucleus, a collection of nerve cells in the hypothalamus.

The current hypothesis is that the KNDy neurons, which communicate with each other, become hyperactivated and cause hot flashes by spilling over to and triggering the thermoregulatory center next door. NKB (kisspeptin and neurokinin B) agonists activate KNDy neurons and dynorphin agonists inactivate KNDy, so the expectation is that NKB antagonists or dynorphin agonists would stop hot flashes.

Indeed, research published in 2015 showed that women taking kappa agonists experienced fewer hot flashes than women in the placebo group. However, no peripherally restricted kappa agonists are currently in clinical trials, so their future as therapeutics is unclear.

Right now, three different NK antagonists are in the pipeline for reducing vasomotor symptoms: MLE 4901 (pavinetant) and ESN364 (fezolinetant) are both NK3R antagonists, and NT-814 is a dual NK1R/NK3R antagonist. All three of these drugs were originally developed to treat schizophrenia.

Phase 2 clinical trials of pavinetant were discontinued in November 2017 by Millendo Therapeutics because 3 of 28 women experienced abnormal liver function, which normalized within 90 days. However, the study had shown an 80% decrease in hot flashes in women taking pavinetant, compared with a 30% decrease in the placebo group.

Fezolinetant, currently in phase 3 trials with Astellas, showed a dose response effect on reproductive hormones in phase 1 studies and a short half-life (4-6 hours) in women. It also showed no concerning side effects.

“There was, in fact, a decrease in the endometrial thickness, a delayed or impeded ovulation and a prolonged cycle duration,” Reed said.

The subsequent phase 2a study showed a reduction of five hot flashes a day (93% decrease), compared with placebo (54% decrease, P <.001) “with an abrupt return to baseline hot flash frequency after cessation,” she said. Improvements also occurred in sleep quality, quality of life, disability, and interference of hot flashes in daily life.

The phase 2b study found no difference in effects between once-daily versus twice-daily doses. However, two severe adverse events occurred: a drug-induced liver injury in one woman and cholelithiasis in another, both on the 60-mg, once-daily dose. Additionally, five women on varying doses had transient increases (above 1000 U/L) in creatinine kinase, though apparently without dose response.

A 52-week, three-arm, phase 3 trial of fezolinetant is currently under way with a goal of enrolling 1,740 participants, and plans to be completed by December 2021. Participants will undergo regular adverse event screening first biweekly, then monthly, with vital signs, blood, and urine monitoring.

Meanwhile, NT-814 from KaNDy Therapeutics, has completed phase 2a and phase 2b trials with phase 3 slated to begin in 2021. Adverse events in phase 1 included sleepiness and headache, and it had a long half-life (about 26 hours) and rapid absorption (an hour).

The phase 2a trial found a reduction of five hot flashes a day, compared with placebo, with main side effects again being sleepiness and headache. No events of abnormal liver function occurred. Phase 2b results have not been published.

So far, existing research suggests that KNDy interventions will involve a single daily oral dose that begins taking effect within 3 days and is fully in effect within 1-2 weeks. The reduction in hot flashes, about five fewer a day, is more effective than any other currently used nonhormonal medications for vasomotor symptoms. SSRIs and SNRIs tend to result in 1.5-2 fewer hot flashes a day, and gabapentin results in about 3 fewer per day. It will take longer-term studies, however, and paying attention to liver concerns for the NK3R antagonists to move into clinic.

“We want to keep our eye on the [luteinizing hormone] because if it decreases too much, it could adversely affect sexual function, and this does appear to be a dose-response finding,” Dr. Reed said. It would also be ideal, she said, to target only the KNDy neurons with NK3 antagonists without effects on the NK3 receptors in the liver.
 

Other nonhormonal options

Oxybutynin is another a nonhormonal agent under investigation for vasomotor symptoms. It’s an anticholinergic that resulted in 80% fewer hot flashes, compared with 30% with placebo in a 2016 trial, but 52% of women complained of dry mouth. A more recent study similarly found high efficacy – a 60%-80% drop in hot flashes, compared with 30% with placebo – but also side effects of dry mouth, difficulty urinating, and abdominal pain.

Finally, Dr. Reed mentioned three other agents under investigation as possible nonhormonal therapeutics, though she has little information about them. They include MT-8554 by Mitsubishi Tanabe; FP-101 by Fervent Pharmaceuticals; and Q-122 by QUE Oncology with Emory University, Atlanta, and the University of Queensland, Brisbane, Australia. 

None of the currently available nonhormonal options provide as high efficacy as hormones, but they do reduce symptoms:

Clonidine is an off-label option some physicians already use as a nonhormonal treatment for vasomotor symptoms, but again, the side effects are problematic: dry mouth, constipation, drowsiness, postural hypotension, and poor sleep.

Paroxetine, at 7.5-10 mg, is the only FDA-approved nonhormonal treatment for vasomotor symptoms, but she listed other off-label options found effective in evidence reviews: gabapentin (100-2,400 mg), venlafaxine (37.5-75 mg), citalopram (10 mg), desvenlafaxine (150 mg), and escitalopram (10 mg).

“I want you to take note of the lower doses in all of these products that are efficacious above those doses that might be used for mood,” Dr. Reed added.

Dr. Reed receives royalties from UpToDate and research funding from Bayer. Dr. Santoro owns stock in MenoGeniX and serves as a consultant or advisor to Ansh Labs, MenoGeniX, and Ogeda/Astellas.

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

The number of heart attack survivors in the United States who experienced repeat attacks within a year decreased between 2008 and 2017, especially among women, yet women’s awareness of their risk of death from heart disease also decreased, according to data from a pair of studies published in Circulation.

Recurrent MI rates drop, but not enough

Although the overall morbidity and mortality from coronary heart disease (CHD) in the United States has been on the decline for decades, CHD remains the leading cause of death and disability in both sexes, wrote Sanne A.E. Peters, PhD, of Imperial College London, and colleagues.

To better assess the rates of recurrent CHD by sex, the researchers reviewed data from 770,408 women and 700,477 men younger than 65 years with commercial health insurance or aged 66 years and older with Medicare who were hospitalized for myocardial infarction between 2008 and 2017. The patients were followed for 1 year for recurrent MIs, recurrent CHD events, heart failure hospitalization, and all-cause mortality.

In the study of recurrent heart disease, the rate of recurrent heart attacks per 1,000 person-years declined from 89.2 to 72.3 in women and from 94.2 to 81.3 in men. In addition, the rate of recurrent heart disease events (defined as either an MI or an artery-opening procedure), dropped per 1,000 person-years from 166.3 to 133.3 in women and from 198.1 to 176.8 in men. The reduction was significantly greater among women compared with men (P < .001 for both recurrent MIs and recurrent CHD events) and the differences by sex were consistent throughout the study period.

However, no significant difference occurred in recurrent MI rates among younger women (aged 21-54 years), or men aged 55-79 years, the researchers noted.

Heart failure rates per 1,000 person-years decreased from 177.4 to 158.1 in women and from 162.9 to 156.1 in men during the study period, and all-cause mortality decreased per 1,000 person-years from 403.2 to 389.5 for women and from 436.1 to 417.9 in men.

Potential contributing factors to the reductions in rates of recurrent events after a heart attack may include improved acute cardiac procedures, in-hospital therapy, and secondary prevention, the researchers noted. In addition, “changes in the type and definition of MI may also have contributed to the decline in recurrent events,” they said. “Also, the introduction and increasing sensitivity of cardiac biomarkers assays, especially cardiac troponin, may have contributed to an increased detection of less severe MIs over time, which, in turn, could have resulted in artifactual reductions in the consequences of MI,” they said.

The study findings were limited by several factors including the use of claims data, lack of information on the severity of heart attacks, and inability to analyze population subgroups, but the results were strengthened by the use of a large, multicultural database.

Despite the decline seen in this study, overall rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality remain high, the researchers said, and the results “highlight the need for interventions to ensure men and women receive guideline recommended treatment to lower the risk for recurrent MI, recurrent CHD, heart failure, and mortality after hospital discharge for MI,” they concluded.

Many women don’t recognize heart disease risk

Although women showed a greater reduction in recurrent MI and recurrent CHD events compared with men, the awareness of heart disease as the No. 1 killer of women has declined, according to a special report from the American Heart Association.

Based on survey data from 2009, 65% of women were aware that heart disease was their leading cause of death (LCOD); by 2019 the number dropped to 44%. The 10-year decline occurred across all races and ethnicities, as well as ages, with the exception of women aged 65 years and older.

The American Heart Association has conducted national surveys since 1997 to monitor awareness of cardiovascular disease among U.S. women. Data from earlier surveys showed increased awareness of heart disease as LCOD and increased awareness of heart attack symptoms between 1997 and 2012, wrote Mary Cushman, MD, of the University of Vermont, Burlington, chair of the writing group for the statement, and colleagues.

Heart disease needs new PR plan

The study of heart disease risk awareness among women was an important update to understand how well the message about women’s risk is getting out, said Martha Gulati, MD, president-elect of the American Society of Preventive Cardiology, in an interview.

The issue remains that heart disease is the No. 1 killer of women, and the decrease in awareness “means we need to amplify our message,” she said.

“I also question whether the symbol of the red dress [for women’s heart disease] is working, and it seems that now is the time to change this symbol,” she emphasized. “I wear a red dress pin on my lab coat and every day someone asks what it means, and no one recognizes it,” she said. “I think ‘Go Red for Women’ is great and part of our outward campaign, but our symbol needs to change to increase the connection and awareness in women,” she said.

What might be a better symbol? Simply, a heart, said Dr. Gulati. But “we need to study whatever is next to really connect with women and make them understand their risk for heart disease,” she added.

“Additionally, we really need to get to minority women,” she said. “We are lagging there, and the survey was conducted in English so it missed many people,” she noted.

Dr. Gulati said she was shocked at how much awareness of heart disease risk has fallen among women, even in those with risk factors such as hypertension, who were 30% less likely to be aware that heart disease remains their leading cause of death. “Younger women as well as very unaware; what this means to me is that our public education efforts need to be amplified,” Dr. Gulati said.

Barriers to educating women about heart disease risk include language and access to affordable screening, Dr. Gulati emphasized. “We need to ensure screening for heart disease is always included as a covered cost for a preventive service,” she said.

“Research needs to be done to identify what works toward educating women about cardiac risk. We need to identify a marketing tool to increase awareness in women. It might be something different for one race versus another,” Dr. Gulati said. “Our messaging needs to improve, but how we improve it needs more than just health care professionals,” she said.
 

Focus on prevention to reduce MI recurrence

“The study regarding recurrent events after MI is important because we really don’t know much about recurrent coronary heart disease after a MI over time,” said Dr. Gulati. These data can be helpful in managing surviving patients and understanding future risk, she said. “But I was surprised to see fewer recurrent events in women, as women still have more heart failure than men even if it has declined with time,” she noted.

Dr. Gulati questioned several aspects of the study and highlighted some of the limitations. “These are claims data, so do they accurately reflect the U.S. population?” she asked. “Remember, this is a study of people who survived a heart attack; those who didn’t survive aren’t included, and that group is more likely to be women, especially women younger than 55 years,” she said.

In addition, Dr. Gulati noted the lack of data on type of heart attack and on treatment adherence or referral to cardiac rehab, as well as lack of data on long-term medication adherence or follow-up care.

Prevention is the key take-home message from both studies, “whether we are talking primary prevention for the heart disease awareness study or secondary prevention for the recurrent heart attack study,” Dr. Gulati said.

The recurrent heart disease study was supported in part by Amgen and the University of Alabama at Birmingham. Lead author Dr. Peters disclosed support from a UK Medical Research Council Skills Development Fellowship with no financial conflicts. Dr. Cushman had no financial conflicts to disclose; several coauthors on the writing committee disclosed relationships with companies including Amarin and Boehringer Ingelheim. Dr. Gulati had no financial conflicts to disclose.
 

SOURCE: Peters SAE et al. Circulation. 2020 Sep 21. doi: 10.1161/CIRCULATIONAHA.120.047065; Cushman M et al. Circulation. 2020 Sep 21. doi: 10.1161/CIR.0000000000000907.

The number of heart attack survivors in the United States who experienced repeat attacks within a year decreased between 2008 and 2017, especially among women, yet women’s awareness of their risk of death from heart disease also decreased, according to data from a pair of studies published in Circulation.

Recurrent MI rates drop, but not enough

Although the overall morbidity and mortality from coronary heart disease (CHD) in the United States has been on the decline for decades, CHD remains the leading cause of death and disability in both sexes, wrote Sanne A.E. Peters, PhD, of Imperial College London, and colleagues.

To better assess the rates of recurrent CHD by sex, the researchers reviewed data from 770,408 women and 700,477 men younger than 65 years with commercial health insurance or aged 66 years and older with Medicare who were hospitalized for myocardial infarction between 2008 and 2017. The patients were followed for 1 year for recurrent MIs, recurrent CHD events, heart failure hospitalization, and all-cause mortality.

In the study of recurrent heart disease, the rate of recurrent heart attacks per 1,000 person-years declined from 89.2 to 72.3 in women and from 94.2 to 81.3 in men. In addition, the rate of recurrent heart disease events (defined as either an MI or an artery-opening procedure), dropped per 1,000 person-years from 166.3 to 133.3 in women and from 198.1 to 176.8 in men. The reduction was significantly greater among women compared with men (P < .001 for both recurrent MIs and recurrent CHD events) and the differences by sex were consistent throughout the study period.

However, no significant difference occurred in recurrent MI rates among younger women (aged 21-54 years), or men aged 55-79 years, the researchers noted.

Heart failure rates per 1,000 person-years decreased from 177.4 to 158.1 in women and from 162.9 to 156.1 in men during the study period, and all-cause mortality decreased per 1,000 person-years from 403.2 to 389.5 for women and from 436.1 to 417.9 in men.

Potential contributing factors to the reductions in rates of recurrent events after a heart attack may include improved acute cardiac procedures, in-hospital therapy, and secondary prevention, the researchers noted. In addition, “changes in the type and definition of MI may also have contributed to the decline in recurrent events,” they said. “Also, the introduction and increasing sensitivity of cardiac biomarkers assays, especially cardiac troponin, may have contributed to an increased detection of less severe MIs over time, which, in turn, could have resulted in artifactual reductions in the consequences of MI,” they said.

The study findings were limited by several factors including the use of claims data, lack of information on the severity of heart attacks, and inability to analyze population subgroups, but the results were strengthened by the use of a large, multicultural database.

Despite the decline seen in this study, overall rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality remain high, the researchers said, and the results “highlight the need for interventions to ensure men and women receive guideline recommended treatment to lower the risk for recurrent MI, recurrent CHD, heart failure, and mortality after hospital discharge for MI,” they concluded.

Many women don’t recognize heart disease risk

Although women showed a greater reduction in recurrent MI and recurrent CHD events compared with men, the awareness of heart disease as the No. 1 killer of women has declined, according to a special report from the American Heart Association.

Based on survey data from 2009, 65% of women were aware that heart disease was their leading cause of death (LCOD); by 2019 the number dropped to 44%. The 10-year decline occurred across all races and ethnicities, as well as ages, with the exception of women aged 65 years and older.

The American Heart Association has conducted national surveys since 1997 to monitor awareness of cardiovascular disease among U.S. women. Data from earlier surveys showed increased awareness of heart disease as LCOD and increased awareness of heart attack symptoms between 1997 and 2012, wrote Mary Cushman, MD, of the University of Vermont, Burlington, chair of the writing group for the statement, and colleagues.

Heart disease needs new PR plan

The study of heart disease risk awareness among women was an important update to understand how well the message about women’s risk is getting out, said Martha Gulati, MD, president-elect of the American Society of Preventive Cardiology, in an interview.

The issue remains that heart disease is the No. 1 killer of women, and the decrease in awareness “means we need to amplify our message,” she said.

“I also question whether the symbol of the red dress [for women’s heart disease] is working, and it seems that now is the time to change this symbol,” she emphasized. “I wear a red dress pin on my lab coat and every day someone asks what it means, and no one recognizes it,” she said. “I think ‘Go Red for Women’ is great and part of our outward campaign, but our symbol needs to change to increase the connection and awareness in women,” she said.

What might be a better symbol? Simply, a heart, said Dr. Gulati. But “we need to study whatever is next to really connect with women and make them understand their risk for heart disease,” she added.

“Additionally, we really need to get to minority women,” she said. “We are lagging there, and the survey was conducted in English so it missed many people,” she noted.

Dr. Gulati said she was shocked at how much awareness of heart disease risk has fallen among women, even in those with risk factors such as hypertension, who were 30% less likely to be aware that heart disease remains their leading cause of death. “Younger women as well as very unaware; what this means to me is that our public education efforts need to be amplified,” Dr. Gulati said.

Barriers to educating women about heart disease risk include language and access to affordable screening, Dr. Gulati emphasized. “We need to ensure screening for heart disease is always included as a covered cost for a preventive service,” she said.

“Research needs to be done to identify what works toward educating women about cardiac risk. We need to identify a marketing tool to increase awareness in women. It might be something different for one race versus another,” Dr. Gulati said. “Our messaging needs to improve, but how we improve it needs more than just health care professionals,” she said.
 

Focus on prevention to reduce MI recurrence

“The study regarding recurrent events after MI is important because we really don’t know much about recurrent coronary heart disease after a MI over time,” said Dr. Gulati. These data can be helpful in managing surviving patients and understanding future risk, she said. “But I was surprised to see fewer recurrent events in women, as women still have more heart failure than men even if it has declined with time,” she noted.

Dr. Gulati questioned several aspects of the study and highlighted some of the limitations. “These are claims data, so do they accurately reflect the U.S. population?” she asked. “Remember, this is a study of people who survived a heart attack; those who didn’t survive aren’t included, and that group is more likely to be women, especially women younger than 55 years,” she said.

In addition, Dr. Gulati noted the lack of data on type of heart attack and on treatment adherence or referral to cardiac rehab, as well as lack of data on long-term medication adherence or follow-up care.

Prevention is the key take-home message from both studies, “whether we are talking primary prevention for the heart disease awareness study or secondary prevention for the recurrent heart attack study,” Dr. Gulati said.

The recurrent heart disease study was supported in part by Amgen and the University of Alabama at Birmingham. Lead author Dr. Peters disclosed support from a UK Medical Research Council Skills Development Fellowship with no financial conflicts. Dr. Cushman had no financial conflicts to disclose; several coauthors on the writing committee disclosed relationships with companies including Amarin and Boehringer Ingelheim. Dr. Gulati had no financial conflicts to disclose.
 

SOURCE: Peters SAE et al. Circulation. 2020 Sep 21. doi: 10.1161/CIRCULATIONAHA.120.047065; Cushman M et al. Circulation. 2020 Sep 21. doi: 10.1161/CIR.0000000000000907.

The number of heart attack survivors in the United States who experienced repeat attacks within a year decreased between 2008 and 2017, especially among women, yet women’s awareness of their risk of death from heart disease also decreased, according to data from a pair of studies published in Circulation.

Recurrent MI rates drop, but not enough

Although the overall morbidity and mortality from coronary heart disease (CHD) in the United States has been on the decline for decades, CHD remains the leading cause of death and disability in both sexes, wrote Sanne A.E. Peters, PhD, of Imperial College London, and colleagues.

To better assess the rates of recurrent CHD by sex, the researchers reviewed data from 770,408 women and 700,477 men younger than 65 years with commercial health insurance or aged 66 years and older with Medicare who were hospitalized for myocardial infarction between 2008 and 2017. The patients were followed for 1 year for recurrent MIs, recurrent CHD events, heart failure hospitalization, and all-cause mortality.

In the study of recurrent heart disease, the rate of recurrent heart attacks per 1,000 person-years declined from 89.2 to 72.3 in women and from 94.2 to 81.3 in men. In addition, the rate of recurrent heart disease events (defined as either an MI or an artery-opening procedure), dropped per 1,000 person-years from 166.3 to 133.3 in women and from 198.1 to 176.8 in men. The reduction was significantly greater among women compared with men (P < .001 for both recurrent MIs and recurrent CHD events) and the differences by sex were consistent throughout the study period.

However, no significant difference occurred in recurrent MI rates among younger women (aged 21-54 years), or men aged 55-79 years, the researchers noted.

Heart failure rates per 1,000 person-years decreased from 177.4 to 158.1 in women and from 162.9 to 156.1 in men during the study period, and all-cause mortality decreased per 1,000 person-years from 403.2 to 389.5 for women and from 436.1 to 417.9 in men.

Potential contributing factors to the reductions in rates of recurrent events after a heart attack may include improved acute cardiac procedures, in-hospital therapy, and secondary prevention, the researchers noted. In addition, “changes in the type and definition of MI may also have contributed to the decline in recurrent events,” they said. “Also, the introduction and increasing sensitivity of cardiac biomarkers assays, especially cardiac troponin, may have contributed to an increased detection of less severe MIs over time, which, in turn, could have resulted in artifactual reductions in the consequences of MI,” they said.

The study findings were limited by several factors including the use of claims data, lack of information on the severity of heart attacks, and inability to analyze population subgroups, but the results were strengthened by the use of a large, multicultural database.

Despite the decline seen in this study, overall rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality remain high, the researchers said, and the results “highlight the need for interventions to ensure men and women receive guideline recommended treatment to lower the risk for recurrent MI, recurrent CHD, heart failure, and mortality after hospital discharge for MI,” they concluded.

Many women don’t recognize heart disease risk

Although women showed a greater reduction in recurrent MI and recurrent CHD events compared with men, the awareness of heart disease as the No. 1 killer of women has declined, according to a special report from the American Heart Association.

Based on survey data from 2009, 65% of women were aware that heart disease was their leading cause of death (LCOD); by 2019 the number dropped to 44%. The 10-year decline occurred across all races and ethnicities, as well as ages, with the exception of women aged 65 years and older.

The American Heart Association has conducted national surveys since 1997 to monitor awareness of cardiovascular disease among U.S. women. Data from earlier surveys showed increased awareness of heart disease as LCOD and increased awareness of heart attack symptoms between 1997 and 2012, wrote Mary Cushman, MD, of the University of Vermont, Burlington, chair of the writing group for the statement, and colleagues.

Heart disease needs new PR plan

The study of heart disease risk awareness among women was an important update to understand how well the message about women’s risk is getting out, said Martha Gulati, MD, president-elect of the American Society of Preventive Cardiology, in an interview.

The issue remains that heart disease is the No. 1 killer of women, and the decrease in awareness “means we need to amplify our message,” she said.

“I also question whether the symbol of the red dress [for women’s heart disease] is working, and it seems that now is the time to change this symbol,” she emphasized. “I wear a red dress pin on my lab coat and every day someone asks what it means, and no one recognizes it,” she said. “I think ‘Go Red for Women’ is great and part of our outward campaign, but our symbol needs to change to increase the connection and awareness in women,” she said.

What might be a better symbol? Simply, a heart, said Dr. Gulati. But “we need to study whatever is next to really connect with women and make them understand their risk for heart disease,” she added.

“Additionally, we really need to get to minority women,” she said. “We are lagging there, and the survey was conducted in English so it missed many people,” she noted.

Dr. Gulati said she was shocked at how much awareness of heart disease risk has fallen among women, even in those with risk factors such as hypertension, who were 30% less likely to be aware that heart disease remains their leading cause of death. “Younger women as well as very unaware; what this means to me is that our public education efforts need to be amplified,” Dr. Gulati said.

Barriers to educating women about heart disease risk include language and access to affordable screening, Dr. Gulati emphasized. “We need to ensure screening for heart disease is always included as a covered cost for a preventive service,” she said.

“Research needs to be done to identify what works toward educating women about cardiac risk. We need to identify a marketing tool to increase awareness in women. It might be something different for one race versus another,” Dr. Gulati said. “Our messaging needs to improve, but how we improve it needs more than just health care professionals,” she said.
 

Focus on prevention to reduce MI recurrence

“The study regarding recurrent events after MI is important because we really don’t know much about recurrent coronary heart disease after a MI over time,” said Dr. Gulati. These data can be helpful in managing surviving patients and understanding future risk, she said. “But I was surprised to see fewer recurrent events in women, as women still have more heart failure than men even if it has declined with time,” she noted.

Dr. Gulati questioned several aspects of the study and highlighted some of the limitations. “These are claims data, so do they accurately reflect the U.S. population?” she asked. “Remember, this is a study of people who survived a heart attack; those who didn’t survive aren’t included, and that group is more likely to be women, especially women younger than 55 years,” she said.

In addition, Dr. Gulati noted the lack of data on type of heart attack and on treatment adherence or referral to cardiac rehab, as well as lack of data on long-term medication adherence or follow-up care.

Prevention is the key take-home message from both studies, “whether we are talking primary prevention for the heart disease awareness study or secondary prevention for the recurrent heart attack study,” Dr. Gulati said.

The recurrent heart disease study was supported in part by Amgen and the University of Alabama at Birmingham. Lead author Dr. Peters disclosed support from a UK Medical Research Council Skills Development Fellowship with no financial conflicts. Dr. Cushman had no financial conflicts to disclose; several coauthors on the writing committee disclosed relationships with companies including Amarin and Boehringer Ingelheim. Dr. Gulati had no financial conflicts to disclose.
 

SOURCE: Peters SAE et al. Circulation. 2020 Sep 21. doi: 10.1161/CIRCULATIONAHA.120.047065; Cushman M et al. Circulation. 2020 Sep 21. doi: 10.1161/CIR.0000000000000907.

The popular new weight-loss approach of eating within a restricted window of time during the day, allowing for an extended period of fasting – also known as intermittent fasting – does not result in greater weight loss, compared with nonrestricted meal timing, results from a randomized clinical trial show.

“I was very surprised by all of [the results],” senior author Ethan J. Weiss, MD, said in an interview.

“Part of the reason we did the study was because I had been doing time-restricted eating myself for years and even recommending it to friends and patients as an effective weight-loss tool,” said Dr. Weiss, of the Cardiovascular Research Institute, University of California, San Francisco.

“But no matter how you slice it, prescription of time-restricted eating – at least this version –is not a very effective weight-loss strategy,” Dr. Weiss said.

The study, published online in JAMA Internal Medicine by Dylan A. Lowe, PhD, also of the University of California, San Francisco, involved 116 participants who were randomized to a 12-week regimen of either three structured meals per day or time-restricted eating, with instructions to eat only between 12:00 p.m. and 8:00 p.m. and to completely abstain from eating at other times.

The participants were not given any specific instructions regarding caloric or macronutrient intake “so as to offer a simple, real-world recommendation to free-living individuals,” the authors wrote.

Although some prior research has shown improvements in measures such as glucose tolerance with time-restricted eating, studies showing weight loss with the approach, including one recently reported by Medscape Medical News, have been small and lacked control groups.

“To my knowledge this is the first randomized, controlled trial and definitely the biggest,” Dr. Weiss. “I think it is the most comprehensive dataset available in people, at least for this intervention.”
 

Participants used app to log details

At baseline, participants had a mean weight of 99.2 kg (approximately 219 lb). Their mean age was 46.5 years and 60.3% were men. They were drawn from anywhere in the United States and received study surveys through a custom mobile study application on the Eureka Research Platform. They were given a Bluetooth weight scale to use daily, which was connected with the app, and randomized to one of the two interventions. A subset of 50 participants living near San Francisco underwent in-person testing.

At the end of the 12 weeks, those in the time-restricted eating group (n = 59) did have a significant decrease in weight, compared with baseline (−0.94 kg; P = .01), while weight loss in the consistent-meal group (n = 57) was not significant (−0.68 kg; P = .07).

But importantly, the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

There were no significant differences in secondary outcomes of fasting insulin, glucose, hemoglobin A1c, or blood lipids within or between the time-restricted eating and consistent-meal group either. Nor were there any significant differences in resting metabolic rate.

Although participants did not self-report their caloric intake, the authors estimated that the differences were not significant using mathematical modeling developed at the National Institutes of Health.

Rates of adherence to the diets were 92.1% in the consistent-meal group versus 83.5% in the time-restricted group.
 

Not all diets are equal: Time-restricted eating group lost more lean mass

In a subset analysis, loss of lean mass was significantly greater in the time-restricted eating group, compared with the consistent-meals group, in terms of both appendicular lean mass (P = .009) and the appendicular lean mass index (P = .005).

In fact, as much as 65% of the weight lost (1.10 kg of the average 1.70 kg) in the time-restricted eating group consisted of lean mass, while much less was fat mass (0.51 kg).

“The proportion of lean mass loss in this study (approximately 65%) far exceeds the normal range of 20%-30%,” the authors wrote. “In addition, there was a highly significant between-group difference in appendicular lean mass.”

Appendicular lean mass correlates with nutritional and physical status, and its reduction can lead to weakness, disability, and impaired quality of life.

“This serves as a caution for patient populations at risk for sarcopenia because time-restricted eating could exacerbate muscle loss,” the authors asserted.

Furthermore, previous studies suggest that the loss of lean mass in such studies is positively linked with weight regain.

While a limitation of the work is that self-reported measures of energy or macronutrient or protein intake were not obtained, the authors speculated that the role of protein intake could be linked to the greater loss of lean mass.

“Given the loss of appendicular lean mass in participants in the time-restricted eating arm and previous reports of decreased protein consumption from time-restricted eating, it is possible that protein intake was altered by time-restricted eating in this cohort, and this clearly warrants future study,” they wrote.

Dr. Weiss said the findings underscore that not all weight loss in dieting is beneficial.

“Losing 1 kg of lean mass (is not equal) to a kilogram of fat,” he said. “Indeed, if one loses 0.65 kg of lean mass and only 0.35 kg of fat mass, that is an intervention I’d probably pass on.”
 

Time-restricted eating is popular, perhaps because it’s easy?

Time-restricted eating has gained popularity in recent years.

The approach “is attractive as a weight-loss option in that it does not require tedious and time-consuming methods such as calorie counting or adherence to complicated diets,” the authors noted. “Indeed, we found that self-reported adherence to the time-restricted eating schedule was high; however, in contrast to our hypothesis, there was no greater weight loss with time-restricted eating compared with the consistent meal timing.”

They explain that the 12 p.m. to 8 p.m. window for eating was chosen because they thought people might find it easier culturally to skip breakfast than dinner, the more social meal.

However, an 8 p.m. cutoff is somewhat late given there is some suggestion that fasting several hours before bedtime is most beneficial, Dr. Weiss noted. So it may be worth examining different time windows.

“I am very intrigued about looking at early time-restricted eating – 6 a.m. to 2 p.m.,” for example, he said. “It is on our list.”

Meanwhile, the study results support previous research showing no effect on weight outcomes in relation to skipping breakfast.

The study received funding from the UCSF cardiology division’s Cardiology Innovations Award Program and the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from the James Peter Read Foundation. Dr. Weiss has reported nonfinancial support from Mocacare and nonfinancial support from iHealth Labs during the conduct of the study. He also is a cofounder and equity stakeholder of Keyto, and owns stock and was formerly on the board of Virta.

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

The popular new weight-loss approach of eating within a restricted window of time during the day, allowing for an extended period of fasting – also known as intermittent fasting – does not result in greater weight loss, compared with nonrestricted meal timing, results from a randomized clinical trial show.

“I was very surprised by all of [the results],” senior author Ethan J. Weiss, MD, said in an interview.

“Part of the reason we did the study was because I had been doing time-restricted eating myself for years and even recommending it to friends and patients as an effective weight-loss tool,” said Dr. Weiss, of the Cardiovascular Research Institute, University of California, San Francisco.

“But no matter how you slice it, prescription of time-restricted eating – at least this version –is not a very effective weight-loss strategy,” Dr. Weiss said.

The study, published online in JAMA Internal Medicine by Dylan A. Lowe, PhD, also of the University of California, San Francisco, involved 116 participants who were randomized to a 12-week regimen of either three structured meals per day or time-restricted eating, with instructions to eat only between 12:00 p.m. and 8:00 p.m. and to completely abstain from eating at other times.

The participants were not given any specific instructions regarding caloric or macronutrient intake “so as to offer a simple, real-world recommendation to free-living individuals,” the authors wrote.

Although some prior research has shown improvements in measures such as glucose tolerance with time-restricted eating, studies showing weight loss with the approach, including one recently reported by Medscape Medical News, have been small and lacked control groups.

“To my knowledge this is the first randomized, controlled trial and definitely the biggest,” Dr. Weiss. “I think it is the most comprehensive dataset available in people, at least for this intervention.”
 

Participants used app to log details

At baseline, participants had a mean weight of 99.2 kg (approximately 219 lb). Their mean age was 46.5 years and 60.3% were men. They were drawn from anywhere in the United States and received study surveys through a custom mobile study application on the Eureka Research Platform. They were given a Bluetooth weight scale to use daily, which was connected with the app, and randomized to one of the two interventions. A subset of 50 participants living near San Francisco underwent in-person testing.

At the end of the 12 weeks, those in the time-restricted eating group (n = 59) did have a significant decrease in weight, compared with baseline (−0.94 kg; P = .01), while weight loss in the consistent-meal group (n = 57) was not significant (−0.68 kg; P = .07).

But importantly, the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

There were no significant differences in secondary outcomes of fasting insulin, glucose, hemoglobin A1c, or blood lipids within or between the time-restricted eating and consistent-meal group either. Nor were there any significant differences in resting metabolic rate.

Although participants did not self-report their caloric intake, the authors estimated that the differences were not significant using mathematical modeling developed at the National Institutes of Health.

Rates of adherence to the diets were 92.1% in the consistent-meal group versus 83.5% in the time-restricted group.
 

Not all diets are equal: Time-restricted eating group lost more lean mass

In a subset analysis, loss of lean mass was significantly greater in the time-restricted eating group, compared with the consistent-meals group, in terms of both appendicular lean mass (P = .009) and the appendicular lean mass index (P = .005).

In fact, as much as 65% of the weight lost (1.10 kg of the average 1.70 kg) in the time-restricted eating group consisted of lean mass, while much less was fat mass (0.51 kg).

“The proportion of lean mass loss in this study (approximately 65%) far exceeds the normal range of 20%-30%,” the authors wrote. “In addition, there was a highly significant between-group difference in appendicular lean mass.”

Appendicular lean mass correlates with nutritional and physical status, and its reduction can lead to weakness, disability, and impaired quality of life.

“This serves as a caution for patient populations at risk for sarcopenia because time-restricted eating could exacerbate muscle loss,” the authors asserted.

Furthermore, previous studies suggest that the loss of lean mass in such studies is positively linked with weight regain.

While a limitation of the work is that self-reported measures of energy or macronutrient or protein intake were not obtained, the authors speculated that the role of protein intake could be linked to the greater loss of lean mass.

“Given the loss of appendicular lean mass in participants in the time-restricted eating arm and previous reports of decreased protein consumption from time-restricted eating, it is possible that protein intake was altered by time-restricted eating in this cohort, and this clearly warrants future study,” they wrote.

Dr. Weiss said the findings underscore that not all weight loss in dieting is beneficial.

“Losing 1 kg of lean mass (is not equal) to a kilogram of fat,” he said. “Indeed, if one loses 0.65 kg of lean mass and only 0.35 kg of fat mass, that is an intervention I’d probably pass on.”
 

Time-restricted eating is popular, perhaps because it’s easy?

Time-restricted eating has gained popularity in recent years.

The approach “is attractive as a weight-loss option in that it does not require tedious and time-consuming methods such as calorie counting or adherence to complicated diets,” the authors noted. “Indeed, we found that self-reported adherence to the time-restricted eating schedule was high; however, in contrast to our hypothesis, there was no greater weight loss with time-restricted eating compared with the consistent meal timing.”

They explain that the 12 p.m. to 8 p.m. window for eating was chosen because they thought people might find it easier culturally to skip breakfast than dinner, the more social meal.

However, an 8 p.m. cutoff is somewhat late given there is some suggestion that fasting several hours before bedtime is most beneficial, Dr. Weiss noted. So it may be worth examining different time windows.

“I am very intrigued about looking at early time-restricted eating – 6 a.m. to 2 p.m.,” for example, he said. “It is on our list.”

Meanwhile, the study results support previous research showing no effect on weight outcomes in relation to skipping breakfast.

The study received funding from the UCSF cardiology division’s Cardiology Innovations Award Program and the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from the James Peter Read Foundation. Dr. Weiss has reported nonfinancial support from Mocacare and nonfinancial support from iHealth Labs during the conduct of the study. He also is a cofounder and equity stakeholder of Keyto, and owns stock and was formerly on the board of Virta.

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

The popular new weight-loss approach of eating within a restricted window of time during the day, allowing for an extended period of fasting – also known as intermittent fasting – does not result in greater weight loss, compared with nonrestricted meal timing, results from a randomized clinical trial show.

“I was very surprised by all of [the results],” senior author Ethan J. Weiss, MD, said in an interview.

“Part of the reason we did the study was because I had been doing time-restricted eating myself for years and even recommending it to friends and patients as an effective weight-loss tool,” said Dr. Weiss, of the Cardiovascular Research Institute, University of California, San Francisco.

“But no matter how you slice it, prescription of time-restricted eating – at least this version –is not a very effective weight-loss strategy,” Dr. Weiss said.

The study, published online in JAMA Internal Medicine by Dylan A. Lowe, PhD, also of the University of California, San Francisco, involved 116 participants who were randomized to a 12-week regimen of either three structured meals per day or time-restricted eating, with instructions to eat only between 12:00 p.m. and 8:00 p.m. and to completely abstain from eating at other times.

The participants were not given any specific instructions regarding caloric or macronutrient intake “so as to offer a simple, real-world recommendation to free-living individuals,” the authors wrote.

Although some prior research has shown improvements in measures such as glucose tolerance with time-restricted eating, studies showing weight loss with the approach, including one recently reported by Medscape Medical News, have been small and lacked control groups.

“To my knowledge this is the first randomized, controlled trial and definitely the biggest,” Dr. Weiss. “I think it is the most comprehensive dataset available in people, at least for this intervention.”
 

Participants used app to log details

At baseline, participants had a mean weight of 99.2 kg (approximately 219 lb). Their mean age was 46.5 years and 60.3% were men. They were drawn from anywhere in the United States and received study surveys through a custom mobile study application on the Eureka Research Platform. They were given a Bluetooth weight scale to use daily, which was connected with the app, and randomized to one of the two interventions. A subset of 50 participants living near San Francisco underwent in-person testing.

At the end of the 12 weeks, those in the time-restricted eating group (n = 59) did have a significant decrease in weight, compared with baseline (−0.94 kg; P = .01), while weight loss in the consistent-meal group (n = 57) was not significant (−0.68 kg; P = .07).

But importantly, the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

There were no significant differences in secondary outcomes of fasting insulin, glucose, hemoglobin A1c, or blood lipids within or between the time-restricted eating and consistent-meal group either. Nor were there any significant differences in resting metabolic rate.

Although participants did not self-report their caloric intake, the authors estimated that the differences were not significant using mathematical modeling developed at the National Institutes of Health.

Rates of adherence to the diets were 92.1% in the consistent-meal group versus 83.5% in the time-restricted group.
 

Not all diets are equal: Time-restricted eating group lost more lean mass

In a subset analysis, loss of lean mass was significantly greater in the time-restricted eating group, compared with the consistent-meals group, in terms of both appendicular lean mass (P = .009) and the appendicular lean mass index (P = .005).

In fact, as much as 65% of the weight lost (1.10 kg of the average 1.70 kg) in the time-restricted eating group consisted of lean mass, while much less was fat mass (0.51 kg).

“The proportion of lean mass loss in this study (approximately 65%) far exceeds the normal range of 20%-30%,” the authors wrote. “In addition, there was a highly significant between-group difference in appendicular lean mass.”

Appendicular lean mass correlates with nutritional and physical status, and its reduction can lead to weakness, disability, and impaired quality of life.

“This serves as a caution for patient populations at risk for sarcopenia because time-restricted eating could exacerbate muscle loss,” the authors asserted.

Furthermore, previous studies suggest that the loss of lean mass in such studies is positively linked with weight regain.

While a limitation of the work is that self-reported measures of energy or macronutrient or protein intake were not obtained, the authors speculated that the role of protein intake could be linked to the greater loss of lean mass.

“Given the loss of appendicular lean mass in participants in the time-restricted eating arm and previous reports of decreased protein consumption from time-restricted eating, it is possible that protein intake was altered by time-restricted eating in this cohort, and this clearly warrants future study,” they wrote.

Dr. Weiss said the findings underscore that not all weight loss in dieting is beneficial.

“Losing 1 kg of lean mass (is not equal) to a kilogram of fat,” he said. “Indeed, if one loses 0.65 kg of lean mass and only 0.35 kg of fat mass, that is an intervention I’d probably pass on.”
 

Time-restricted eating is popular, perhaps because it’s easy?

Time-restricted eating has gained popularity in recent years.

The approach “is attractive as a weight-loss option in that it does not require tedious and time-consuming methods such as calorie counting or adherence to complicated diets,” the authors noted. “Indeed, we found that self-reported adherence to the time-restricted eating schedule was high; however, in contrast to our hypothesis, there was no greater weight loss with time-restricted eating compared with the consistent meal timing.”

They explain that the 12 p.m. to 8 p.m. window for eating was chosen because they thought people might find it easier culturally to skip breakfast than dinner, the more social meal.

However, an 8 p.m. cutoff is somewhat late given there is some suggestion that fasting several hours before bedtime is most beneficial, Dr. Weiss noted. So it may be worth examining different time windows.

“I am very intrigued about looking at early time-restricted eating – 6 a.m. to 2 p.m.,” for example, he said. “It is on our list.”

Meanwhile, the study results support previous research showing no effect on weight outcomes in relation to skipping breakfast.

The study received funding from the UCSF cardiology division’s Cardiology Innovations Award Program and the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from the James Peter Read Foundation. Dr. Weiss has reported nonfinancial support from Mocacare and nonfinancial support from iHealth Labs during the conduct of the study. He also is a cofounder and equity stakeholder of Keyto, and owns stock and was formerly on the board of Virta.

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

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

mzoler@mdedge.com

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

mzoler@mdedge.com

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

mzoler@mdedge.com

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how that would be put into practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Randomized, controlled trials or many more observational studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the current study don’t warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how that would be put into practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Randomized, controlled trials or many more observational studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the current study don’t warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how that would be put into practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Randomized, controlled trials or many more observational studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the current study don’t warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

Stroke may be the first presenting symptom of COVID-19 in younger patients, new research suggests. Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Although younger patients had the highest risk of stroke, the highest risk of death was in patients who were older, had other chronic conditions, and had more severe COVID-19–associated respiratory symptoms.

“One of the most eye-opening findings of this study is that, for patients under 50 years old, many were totally asymptomatic when they had a stroke related to COVID-19, [which] means that, for these patients, the stroke was their first symptom of the disease,” lead author Luciano Sposato, MD, MBA, associate professor and chair in stroke research at Western University, London, Ont.

The study was published online Sept. 15 in Neurology.
 

Anecdotal reports

“In early April of 2020, we realized that COVID-19 was a highly thrombogenic disease,” said Dr. Sposato. “Almost in parallel, I started to see anecdotal reports in social media of strokes occurring in patients with COVID-19, and there were also very few case reports.”

The investigators “thought it would be a good idea to put all the data together in one paper,” he said, and began by conducting a systematic review of 10 published studies of COVID-19 and stroke (n = 125 patients), which were then pooled with 35 unpublished cases from Canada, the United States, and Iran for a total of 160 cases.

The analysis examined in-hospital mortality rates of patients with stroke and COVID-19.

In addition, the researchers conducted a second review of 150 papers, encompassing a final cohort of 3,306 COVID-19 patients with stroke of any type and 5,322 with ischemic stroke.

“Some studies reported data for only ischemic stroke, and some reported data for all strokes considered together, which resulted in a different number of patients on each meta-analysis, with a lower number of ‘any stroke’ cases,” Dr. Sposato explained. “This review looked at the number of patients who developed a stroke during admission and included thousands of patients.”

Dr. Sposato noted that the first review was conducted on single case reports and small case series “to understand the clinical characteristics of strokes in patients with COVID-19 on an individual patient level,” since “large studies, including hundreds of thousands of patients, usually do not provide the level of detail for a descriptive analysis of the clinical characteristics of a disease.”

Cluster analyses were used to “identify specific clinical phenotypes and their relationship with death.” Patients were stratified into three age groups: <50, 50-70, and >70 years (“young,” “middle aged,” and “older,” respectively). The median age was 65 years and 43% were female.
 

Mortality ‘remarkably high’

The review showed that 1.8% (95% confidence interval, 0.9%-3.7%) of patients experienced a new stroke, while 1.5% (95% CI, 0.8%-2.8%) of these experienced an ischemic stroke. “These numbers are higher than historical data for other infectious diseases – for example, 0.75% in SARS-CoV-1, 0.78% in sepsis, and 0.2% in influenza,” Dr. Sposato commented.

Moreover, “this number may be an underestimate, given that many patients die without a confirmed diagnosis and that some patients did not come to the emergency department when experiencing mild symptoms during the first months of the pandemic,” he added.

Focusing on the review of 160 patients, the researchers described in-hospital mortality for strokes of all types and for ischemic strokes alone as “remarkably high” (34.4% [95% CI, 27.2%-42.4%] and 35.7% [95% CI, 27.5%-44.8%], respectively), with most deaths occurring among ischemic stroke patients.

“This high mortality rate is higher than the [roughly] 15% to 30% reported for stroke patients without COVID-19 admitted to intensive care units,” Dr. Sposato said.
 

High-risk phenotype

Many “young” COVID-19 patients (under age 50) who had a stroke (42.9%) had no previous risk factors or comorbidities. Moreover, in almost half of these patients (48.3%), stroke was more likely to occur before the onset of any COVID-19 respiratory symptoms.

Additionally, younger patients showed the highest frequency of elevated cardiac troponin compared with middle-aged and older patients (71.4% vs. 48.4% and 27.8%, respectively). On the other hand, mortality was 67% lower in younger versus older patients (odds ratio, 0.33; 95% CI, 0.12-0.94; P = .039).

Dr. Sposato noted that the proportion of ischemic stroke patients with large-vessel occlusion was “higher than previously reported” for patients with stroke without COVID-19 (47% compared with 29%, respectively).

“We should consider COVID-19 as a new cause or risk factor for stroke. At least, patients with stroke should probably be tested for SARS-CoV-2 infection if they are young and present with a large-vessel occlusion, even in the absence of typical COVID-19 respiratory symptoms,” he suggested.

The researchers identified a “high-risk phenotype” for death for all types of stroke considered together: older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms. Patients with all three characteristics had the highest in-hospital mortality rate (58.6%) and a threefold risk of death, compared with the rest of the cohort (OR, 3.52; 95% CI, 1.53-8.09; P = .003).

“Several potential mechanisms can explain the increased risk of stroke among COVID-19 patients, but perhaps the most important one is increased thrombogenesis secondary to an exaggerated inflammatory response,” Dr. Sposato said.
 

Not just elders

Commenting on the study, Jodi Edwards, PhD, director of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute, said the findings are “consistent with and underscore public health messaging emphasizing that COVID-19 does not only affect the elderly and those with underlying health conditions, but can have serious and even fatal consequences at any age.”

Dr. Edwards, who was not involved with the study, emphasized that “adherence to public health recommendations is critical to begin to reduce the rising incidence in younger adults.”

Dr. Sposato acknowledged that the study was small and that there “can be problems associated with a systematic review of case reports, such as publication bias, lack of completeness of data, etc, so more research is needed.”

Dr. Sposato is supported by the Kathleen & Dr. Henry Barnett Research Chair in Stroke Research at Western University, the Edward and Alma Saraydar Neurosciences Fund of the London Health Sciences Foundation, and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario. Dr. Sposato reported speaker honoraria from Boehringer Ingelheim, Pfizer, Gore, and Bayer and research/quality improvement grants from Boehringer Ingelheim and Bayer. The other authors’ disclosures are listed on the original article. Dr. Edwards has disclosed no relevant financial relationships.

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

Stroke may be the first presenting symptom of COVID-19 in younger patients, new research suggests. Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Although younger patients had the highest risk of stroke, the highest risk of death was in patients who were older, had other chronic conditions, and had more severe COVID-19–associated respiratory symptoms.

“One of the most eye-opening findings of this study is that, for patients under 50 years old, many were totally asymptomatic when they had a stroke related to COVID-19, [which] means that, for these patients, the stroke was their first symptom of the disease,” lead author Luciano Sposato, MD, MBA, associate professor and chair in stroke research at Western University, London, Ont.

The study was published online Sept. 15 in Neurology.
 

Anecdotal reports

“In early April of 2020, we realized that COVID-19 was a highly thrombogenic disease,” said Dr. Sposato. “Almost in parallel, I started to see anecdotal reports in social media of strokes occurring in patients with COVID-19, and there were also very few case reports.”

The investigators “thought it would be a good idea to put all the data together in one paper,” he said, and began by conducting a systematic review of 10 published studies of COVID-19 and stroke (n = 125 patients), which were then pooled with 35 unpublished cases from Canada, the United States, and Iran for a total of 160 cases.

The analysis examined in-hospital mortality rates of patients with stroke and COVID-19.

In addition, the researchers conducted a second review of 150 papers, encompassing a final cohort of 3,306 COVID-19 patients with stroke of any type and 5,322 with ischemic stroke.

“Some studies reported data for only ischemic stroke, and some reported data for all strokes considered together, which resulted in a different number of patients on each meta-analysis, with a lower number of ‘any stroke’ cases,” Dr. Sposato explained. “This review looked at the number of patients who developed a stroke during admission and included thousands of patients.”

Dr. Sposato noted that the first review was conducted on single case reports and small case series “to understand the clinical characteristics of strokes in patients with COVID-19 on an individual patient level,” since “large studies, including hundreds of thousands of patients, usually do not provide the level of detail for a descriptive analysis of the clinical characteristics of a disease.”

Cluster analyses were used to “identify specific clinical phenotypes and their relationship with death.” Patients were stratified into three age groups: <50, 50-70, and >70 years (“young,” “middle aged,” and “older,” respectively). The median age was 65 years and 43% were female.
 

Mortality ‘remarkably high’

The review showed that 1.8% (95% confidence interval, 0.9%-3.7%) of patients experienced a new stroke, while 1.5% (95% CI, 0.8%-2.8%) of these experienced an ischemic stroke. “These numbers are higher than historical data for other infectious diseases – for example, 0.75% in SARS-CoV-1, 0.78% in sepsis, and 0.2% in influenza,” Dr. Sposato commented.

Moreover, “this number may be an underestimate, given that many patients die without a confirmed diagnosis and that some patients did not come to the emergency department when experiencing mild symptoms during the first months of the pandemic,” he added.

Focusing on the review of 160 patients, the researchers described in-hospital mortality for strokes of all types and for ischemic strokes alone as “remarkably high” (34.4% [95% CI, 27.2%-42.4%] and 35.7% [95% CI, 27.5%-44.8%], respectively), with most deaths occurring among ischemic stroke patients.

“This high mortality rate is higher than the [roughly] 15% to 30% reported for stroke patients without COVID-19 admitted to intensive care units,” Dr. Sposato said.
 

High-risk phenotype

Many “young” COVID-19 patients (under age 50) who had a stroke (42.9%) had no previous risk factors or comorbidities. Moreover, in almost half of these patients (48.3%), stroke was more likely to occur before the onset of any COVID-19 respiratory symptoms.

Additionally, younger patients showed the highest frequency of elevated cardiac troponin compared with middle-aged and older patients (71.4% vs. 48.4% and 27.8%, respectively). On the other hand, mortality was 67% lower in younger versus older patients (odds ratio, 0.33; 95% CI, 0.12-0.94; P = .039).

Dr. Sposato noted that the proportion of ischemic stroke patients with large-vessel occlusion was “higher than previously reported” for patients with stroke without COVID-19 (47% compared with 29%, respectively).

“We should consider COVID-19 as a new cause or risk factor for stroke. At least, patients with stroke should probably be tested for SARS-CoV-2 infection if they are young and present with a large-vessel occlusion, even in the absence of typical COVID-19 respiratory symptoms,” he suggested.

The researchers identified a “high-risk phenotype” for death for all types of stroke considered together: older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms. Patients with all three characteristics had the highest in-hospital mortality rate (58.6%) and a threefold risk of death, compared with the rest of the cohort (OR, 3.52; 95% CI, 1.53-8.09; P = .003).

“Several potential mechanisms can explain the increased risk of stroke among COVID-19 patients, but perhaps the most important one is increased thrombogenesis secondary to an exaggerated inflammatory response,” Dr. Sposato said.
 

Not just elders

Commenting on the study, Jodi Edwards, PhD, director of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute, said the findings are “consistent with and underscore public health messaging emphasizing that COVID-19 does not only affect the elderly and those with underlying health conditions, but can have serious and even fatal consequences at any age.”

Dr. Edwards, who was not involved with the study, emphasized that “adherence to public health recommendations is critical to begin to reduce the rising incidence in younger adults.”

Dr. Sposato acknowledged that the study was small and that there “can be problems associated with a systematic review of case reports, such as publication bias, lack of completeness of data, etc, so more research is needed.”

Dr. Sposato is supported by the Kathleen & Dr. Henry Barnett Research Chair in Stroke Research at Western University, the Edward and Alma Saraydar Neurosciences Fund of the London Health Sciences Foundation, and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario. Dr. Sposato reported speaker honoraria from Boehringer Ingelheim, Pfizer, Gore, and Bayer and research/quality improvement grants from Boehringer Ingelheim and Bayer. The other authors’ disclosures are listed on the original article. Dr. Edwards has disclosed no relevant financial relationships.

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

Stroke may be the first presenting symptom of COVID-19 in younger patients, new research suggests. Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Although younger patients had the highest risk of stroke, the highest risk of death was in patients who were older, had other chronic conditions, and had more severe COVID-19–associated respiratory symptoms.

“One of the most eye-opening findings of this study is that, for patients under 50 years old, many were totally asymptomatic when they had a stroke related to COVID-19, [which] means that, for these patients, the stroke was their first symptom of the disease,” lead author Luciano Sposato, MD, MBA, associate professor and chair in stroke research at Western University, London, Ont.

The study was published online Sept. 15 in Neurology.
 

Anecdotal reports

“In early April of 2020, we realized that COVID-19 was a highly thrombogenic disease,” said Dr. Sposato. “Almost in parallel, I started to see anecdotal reports in social media of strokes occurring in patients with COVID-19, and there were also very few case reports.”

The investigators “thought it would be a good idea to put all the data together in one paper,” he said, and began by conducting a systematic review of 10 published studies of COVID-19 and stroke (n = 125 patients), which were then pooled with 35 unpublished cases from Canada, the United States, and Iran for a total of 160 cases.

The analysis examined in-hospital mortality rates of patients with stroke and COVID-19.

In addition, the researchers conducted a second review of 150 papers, encompassing a final cohort of 3,306 COVID-19 patients with stroke of any type and 5,322 with ischemic stroke.

“Some studies reported data for only ischemic stroke, and some reported data for all strokes considered together, which resulted in a different number of patients on each meta-analysis, with a lower number of ‘any stroke’ cases,” Dr. Sposato explained. “This review looked at the number of patients who developed a stroke during admission and included thousands of patients.”

Dr. Sposato noted that the first review was conducted on single case reports and small case series “to understand the clinical characteristics of strokes in patients with COVID-19 on an individual patient level,” since “large studies, including hundreds of thousands of patients, usually do not provide the level of detail for a descriptive analysis of the clinical characteristics of a disease.”

Cluster analyses were used to “identify specific clinical phenotypes and their relationship with death.” Patients were stratified into three age groups: <50, 50-70, and >70 years (“young,” “middle aged,” and “older,” respectively). The median age was 65 years and 43% were female.
 

Mortality ‘remarkably high’

The review showed that 1.8% (95% confidence interval, 0.9%-3.7%) of patients experienced a new stroke, while 1.5% (95% CI, 0.8%-2.8%) of these experienced an ischemic stroke. “These numbers are higher than historical data for other infectious diseases – for example, 0.75% in SARS-CoV-1, 0.78% in sepsis, and 0.2% in influenza,” Dr. Sposato commented.

Moreover, “this number may be an underestimate, given that many patients die without a confirmed diagnosis and that some patients did not come to the emergency department when experiencing mild symptoms during the first months of the pandemic,” he added.

Focusing on the review of 160 patients, the researchers described in-hospital mortality for strokes of all types and for ischemic strokes alone as “remarkably high” (34.4% [95% CI, 27.2%-42.4%] and 35.7% [95% CI, 27.5%-44.8%], respectively), with most deaths occurring among ischemic stroke patients.

“This high mortality rate is higher than the [roughly] 15% to 30% reported for stroke patients without COVID-19 admitted to intensive care units,” Dr. Sposato said.
 

High-risk phenotype

Many “young” COVID-19 patients (under age 50) who had a stroke (42.9%) had no previous risk factors or comorbidities. Moreover, in almost half of these patients (48.3%), stroke was more likely to occur before the onset of any COVID-19 respiratory symptoms.

Additionally, younger patients showed the highest frequency of elevated cardiac troponin compared with middle-aged and older patients (71.4% vs. 48.4% and 27.8%, respectively). On the other hand, mortality was 67% lower in younger versus older patients (odds ratio, 0.33; 95% CI, 0.12-0.94; P = .039).

Dr. Sposato noted that the proportion of ischemic stroke patients with large-vessel occlusion was “higher than previously reported” for patients with stroke without COVID-19 (47% compared with 29%, respectively).

“We should consider COVID-19 as a new cause or risk factor for stroke. At least, patients with stroke should probably be tested for SARS-CoV-2 infection if they are young and present with a large-vessel occlusion, even in the absence of typical COVID-19 respiratory symptoms,” he suggested.

The researchers identified a “high-risk phenotype” for death for all types of stroke considered together: older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms. Patients with all three characteristics had the highest in-hospital mortality rate (58.6%) and a threefold risk of death, compared with the rest of the cohort (OR, 3.52; 95% CI, 1.53-8.09; P = .003).

“Several potential mechanisms can explain the increased risk of stroke among COVID-19 patients, but perhaps the most important one is increased thrombogenesis secondary to an exaggerated inflammatory response,” Dr. Sposato said.
 

Not just elders

Commenting on the study, Jodi Edwards, PhD, director of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute, said the findings are “consistent with and underscore public health messaging emphasizing that COVID-19 does not only affect the elderly and those with underlying health conditions, but can have serious and even fatal consequences at any age.”

Dr. Edwards, who was not involved with the study, emphasized that “adherence to public health recommendations is critical to begin to reduce the rising incidence in younger adults.”

Dr. Sposato acknowledged that the study was small and that there “can be problems associated with a systematic review of case reports, such as publication bias, lack of completeness of data, etc, so more research is needed.”

Dr. Sposato is supported by the Kathleen & Dr. Henry Barnett Research Chair in Stroke Research at Western University, the Edward and Alma Saraydar Neurosciences Fund of the London Health Sciences Foundation, and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario. Dr. Sposato reported speaker honoraria from Boehringer Ingelheim, Pfizer, Gore, and Bayer and research/quality improvement grants from Boehringer Ingelheim and Bayer. The other authors’ disclosures are listed on the original article. Dr. Edwards has disclosed no relevant financial relationships.

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

The Centers for Disease Control and Prevention acknowledged Oct. 5 in updated guidance that COVID-19 can sometimes be spread through the air, especially in enclosed spaces with poor ventilation, when people are more than 6 feet apart.

The information reiterates, however, that “COVID-19 is thought to spread mainly through close contact from person to person, including between people who are physically near each other (within about 6 feet). People who are infected but do not show symptoms can also spread the virus to others.”

In a statement to the media, the CDC said, “Today’s update acknowledges the existence of some published reports showing limited, uncommon circumstances where people with COVID-19 infected others who were more than 6 feet away or shortly after the COVID-19–positive person left an area. In these instances, transmission occurred in poorly ventilated and enclosed spaces that often involved activities that caused heavier breathing, like singing or exercise. Such environments and activities may contribute to the buildup of virus-carrying particles.”

“This is HUGE and been long delayed. But glad it’s now CDC official,” tweeted Eric Feigl-Ding, MD, an epidemiologist and health economist at Harvard University, Boston on Oct. 5.

The CDC announcement follows an abrupt flip-flop on information last month surrounding the aerosol spread of the virus.
 

Information deleted from website last month

On September 18, the CDC had added to its existing guidance that the virus is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection.”

The CDC then deleted that guidance on Sept. 21, saying it was a draft update released in error.

A key element of the now-deleted guidance said, “this is thought to be the main way the virus spreads.”

The information updated today reverses the now-deleted guidance and says aerosol transmission is not the main way the virus spreads.

It states that people who are within 6 feet of a person with COVID-19 or have direct contact with that person have the greatest risk of infection.

The CDC reiterated in the statement to the media today, “People can protect themselves from the virus that causes COVID-19 by staying at least 6 feet away from others, wearing a mask that covers their nose and mouth, washing their hands frequently, cleaning touched surfaces often, and staying home when sick.”

Among the journals that have published evidence on aerosol spread is Clinical Infectious Diseases, which, on July 6, published the paper, “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors wrote, “there is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).”

Aerosols and airborne transmission “are the only way to explain super-spreader events we are seeing,” said Kimberly Prather, PhD, an atmospheric chemist at the University of California at San Diego, in an interview Oct. 5 with the Washington Post.

Dr. Prather added that, once aerosolization is acknowledged, this becomes a “fixable” problem through proper ventilation.

“Wear masks at all times indoors when others are present,” Dr. Prather said. But when inside, she said, there’s no such thing as a completely safe social distance.

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention acknowledged Oct. 5 in updated guidance that COVID-19 can sometimes be spread through the air, especially in enclosed spaces with poor ventilation, when people are more than 6 feet apart.

The information reiterates, however, that “COVID-19 is thought to spread mainly through close contact from person to person, including between people who are physically near each other (within about 6 feet). People who are infected but do not show symptoms can also spread the virus to others.”

In a statement to the media, the CDC said, “Today’s update acknowledges the existence of some published reports showing limited, uncommon circumstances where people with COVID-19 infected others who were more than 6 feet away or shortly after the COVID-19–positive person left an area. In these instances, transmission occurred in poorly ventilated and enclosed spaces that often involved activities that caused heavier breathing, like singing or exercise. Such environments and activities may contribute to the buildup of virus-carrying particles.”

“This is HUGE and been long delayed. But glad it’s now CDC official,” tweeted Eric Feigl-Ding, MD, an epidemiologist and health economist at Harvard University, Boston on Oct. 5.

The CDC announcement follows an abrupt flip-flop on information last month surrounding the aerosol spread of the virus.
 

Information deleted from website last month

On September 18, the CDC had added to its existing guidance that the virus is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection.”

The CDC then deleted that guidance on Sept. 21, saying it was a draft update released in error.

A key element of the now-deleted guidance said, “this is thought to be the main way the virus spreads.”

The information updated today reverses the now-deleted guidance and says aerosol transmission is not the main way the virus spreads.

It states that people who are within 6 feet of a person with COVID-19 or have direct contact with that person have the greatest risk of infection.

The CDC reiterated in the statement to the media today, “People can protect themselves from the virus that causes COVID-19 by staying at least 6 feet away from others, wearing a mask that covers their nose and mouth, washing their hands frequently, cleaning touched surfaces often, and staying home when sick.”

Among the journals that have published evidence on aerosol spread is Clinical Infectious Diseases, which, on July 6, published the paper, “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors wrote, “there is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).”

Aerosols and airborne transmission “are the only way to explain super-spreader events we are seeing,” said Kimberly Prather, PhD, an atmospheric chemist at the University of California at San Diego, in an interview Oct. 5 with the Washington Post.

Dr. Prather added that, once aerosolization is acknowledged, this becomes a “fixable” problem through proper ventilation.

“Wear masks at all times indoors when others are present,” Dr. Prather said. But when inside, she said, there’s no such thing as a completely safe social distance.

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention acknowledged Oct. 5 in updated guidance that COVID-19 can sometimes be spread through the air, especially in enclosed spaces with poor ventilation, when people are more than 6 feet apart.

The information reiterates, however, that “COVID-19 is thought to spread mainly through close contact from person to person, including between people who are physically near each other (within about 6 feet). People who are infected but do not show symptoms can also spread the virus to others.”

In a statement to the media, the CDC said, “Today’s update acknowledges the existence of some published reports showing limited, uncommon circumstances where people with COVID-19 infected others who were more than 6 feet away or shortly after the COVID-19–positive person left an area. In these instances, transmission occurred in poorly ventilated and enclosed spaces that often involved activities that caused heavier breathing, like singing or exercise. Such environments and activities may contribute to the buildup of virus-carrying particles.”

“This is HUGE and been long delayed. But glad it’s now CDC official,” tweeted Eric Feigl-Ding, MD, an epidemiologist and health economist at Harvard University, Boston on Oct. 5.

The CDC announcement follows an abrupt flip-flop on information last month surrounding the aerosol spread of the virus.
 

Information deleted from website last month

On September 18, the CDC had added to its existing guidance that the virus is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection.”

The CDC then deleted that guidance on Sept. 21, saying it was a draft update released in error.

A key element of the now-deleted guidance said, “this is thought to be the main way the virus spreads.”

The information updated today reverses the now-deleted guidance and says aerosol transmission is not the main way the virus spreads.

It states that people who are within 6 feet of a person with COVID-19 or have direct contact with that person have the greatest risk of infection.

The CDC reiterated in the statement to the media today, “People can protect themselves from the virus that causes COVID-19 by staying at least 6 feet away from others, wearing a mask that covers their nose and mouth, washing their hands frequently, cleaning touched surfaces often, and staying home when sick.”

Among the journals that have published evidence on aerosol spread is Clinical Infectious Diseases, which, on July 6, published the paper, “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors wrote, “there is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).”

Aerosols and airborne transmission “are the only way to explain super-spreader events we are seeing,” said Kimberly Prather, PhD, an atmospheric chemist at the University of California at San Diego, in an interview Oct. 5 with the Washington Post.

Dr. Prather added that, once aerosolization is acknowledged, this becomes a “fixable” problem through proper ventilation.

“Wear masks at all times indoors when others are present,” Dr. Prather said. But when inside, she said, there’s no such thing as a completely safe social distance.

This article first appeared on Medscape.com.

Black and Hispanic children comprised significantly more cases of COVID-19, compared with White children, based on data from a large, cross-sectional study of 1,000 cases.

“Data regarding disparities in SARS-CoV-2 infection and outcomes have been, thus far, mostly limited to adults,” wrote Monika K. Goyal, MD, of Children’s National Hospital, Washington, and colleagues. “Additional data further suggest that low socioeconomic status may further exacerbate health outcomes for racial and ethnic minorities.”

In a study published in Pediatrics, the researchers conducted a cross-sectional analysis of 1,000 children from a registry of non–acutely ill pediatric patients seen at a drive-through and walk-up COVID-19 test site.
 

Minority, socioeconomic status affect pediatric outcomes too

Overall, 207 (21%) of the children tested positive for COVID-19; of these 46% were Hispanic, 30% were non-Hispanic Black, and 7% were non-Hispanic White. The median age of the study population was 8 years, and approximately half were male.

The researchers also examined the association of median family income (MFI) using census block group estimates data from the American Community Survey (2014–2018) to represent socioeconomic status.

Infection rates were significantly higher among children in the lowest three quartiles of MFI (24%, 27%, and 38% for quartiles 3, 2, and 1, respectively), compared with the highest quartile of MFI (9%).

After adjusting for age, sex, and MFI, Hispanic children were six times more likely and non-Hispanic Black children were twice as likely to test positive for COVID-19 than non-Hispanic White children (adjusted odds ratios, 6.3 and 2.3, respectively).

The study findings were limited by several factors including the use of clinician-reported ethnicity and thus potential for misclassification, the researchers noted. In addition, the socioeconomic and racial disparities may be underestimated because these groups have less access to primary care, and the study did not allow for confounding variables including housing conditions or occupancy.

“Although it was beyond the scope of this study to understand the causes for these differential rates of infection, the causes may be multifactorial, including, but not limited to, structural factors, poorer access to health care, limited resources, and bias and discrimination,” the researchers noted. In addition, the high infection rate among minority children may be impacted by parents who are less able to telework, find child care, or avoid public transportation, Dr. Goyal and associates wrote.

Future research should address “the modifiable reasons for these observed disparities as well as their differential impact in terms of SARS-CoV-2–related morbidity and mortality outcomes to mitigate the spread of infection and its health effects,” they concluded.
 

How to help

“This study is important because we need to understand which groups of children are at highest risk for SARS-CoV-2 infection in order to maximize efforts for screening, allocating resources, and prioritizing vaccine administration,” Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was not surprised at the higher infection rates in general in minorities and low socioeconomic groups. “We already knew that adult COVID-19 rates were higher for people in certain racial/ethnic groups and those with socioeconomic disadvantages; however, I was shocked by the percentages. That is a huge burden for a population that already has disparities in health outcomes.”

“As the authors cite, this was not a research study of why these groups were more likely to be COVID-19 positive, but they speculated that crowded living conditions, multigenerational families living together, and many minorities being essential workers unable to work from home,” said Dr. Kinsella. Additional factors contributing to higher infection rates may include limited access to care, transportation issues, insurance coverage, schedule challenges, and fear of deportation. Some of these problems might be addressed by coming into communities in mobile vans, visiting community health centers and schools with free educational materials, using masks and hand sanitizer, and offering free access to testing.

“Future studies could confirm the cause of this discrepancy, as well as study community-based interventions and their outcomes,” Dr. Kinsella said. In the meantime, a take-home message for clinicians is the need to prioritize screening, resources, and vaccines to reflect the higher rates of SARS-CoV-2 infections in children from disadvantaged racial and socioeconomic backgrounds.

The study received no outside funding. The researchers had no financial conflicts to disclose, but lead author Dr. Goyal is a member of the Pediatrics editorial board. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News editorial advisory board.

SOURCE: Goyal MK et al. Pediatrics. 2020 Sep 24. doi: 10.1542/peds.2020-009951.

Black and Hispanic children comprised significantly more cases of COVID-19, compared with White children, based on data from a large, cross-sectional study of 1,000 cases.

“Data regarding disparities in SARS-CoV-2 infection and outcomes have been, thus far, mostly limited to adults,” wrote Monika K. Goyal, MD, of Children’s National Hospital, Washington, and colleagues. “Additional data further suggest that low socioeconomic status may further exacerbate health outcomes for racial and ethnic minorities.”

In a study published in Pediatrics, the researchers conducted a cross-sectional analysis of 1,000 children from a registry of non–acutely ill pediatric patients seen at a drive-through and walk-up COVID-19 test site.
 

Minority, socioeconomic status affect pediatric outcomes too

Overall, 207 (21%) of the children tested positive for COVID-19; of these 46% were Hispanic, 30% were non-Hispanic Black, and 7% were non-Hispanic White. The median age of the study population was 8 years, and approximately half were male.

The researchers also examined the association of median family income (MFI) using census block group estimates data from the American Community Survey (2014–2018) to represent socioeconomic status.

Infection rates were significantly higher among children in the lowest three quartiles of MFI (24%, 27%, and 38% for quartiles 3, 2, and 1, respectively), compared with the highest quartile of MFI (9%).

After adjusting for age, sex, and MFI, Hispanic children were six times more likely and non-Hispanic Black children were twice as likely to test positive for COVID-19 than non-Hispanic White children (adjusted odds ratios, 6.3 and 2.3, respectively).

The study findings were limited by several factors including the use of clinician-reported ethnicity and thus potential for misclassification, the researchers noted. In addition, the socioeconomic and racial disparities may be underestimated because these groups have less access to primary care, and the study did not allow for confounding variables including housing conditions or occupancy.

“Although it was beyond the scope of this study to understand the causes for these differential rates of infection, the causes may be multifactorial, including, but not limited to, structural factors, poorer access to health care, limited resources, and bias and discrimination,” the researchers noted. In addition, the high infection rate among minority children may be impacted by parents who are less able to telework, find child care, or avoid public transportation, Dr. Goyal and associates wrote.

Future research should address “the modifiable reasons for these observed disparities as well as their differential impact in terms of SARS-CoV-2–related morbidity and mortality outcomes to mitigate the spread of infection and its health effects,” they concluded.
 

How to help

“This study is important because we need to understand which groups of children are at highest risk for SARS-CoV-2 infection in order to maximize efforts for screening, allocating resources, and prioritizing vaccine administration,” Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was not surprised at the higher infection rates in general in minorities and low socioeconomic groups. “We already knew that adult COVID-19 rates were higher for people in certain racial/ethnic groups and those with socioeconomic disadvantages; however, I was shocked by the percentages. That is a huge burden for a population that already has disparities in health outcomes.”

“As the authors cite, this was not a research study of why these groups were more likely to be COVID-19 positive, but they speculated that crowded living conditions, multigenerational families living together, and many minorities being essential workers unable to work from home,” said Dr. Kinsella. Additional factors contributing to higher infection rates may include limited access to care, transportation issues, insurance coverage, schedule challenges, and fear of deportation. Some of these problems might be addressed by coming into communities in mobile vans, visiting community health centers and schools with free educational materials, using masks and hand sanitizer, and offering free access to testing.

“Future studies could confirm the cause of this discrepancy, as well as study community-based interventions and their outcomes,” Dr. Kinsella said. In the meantime, a take-home message for clinicians is the need to prioritize screening, resources, and vaccines to reflect the higher rates of SARS-CoV-2 infections in children from disadvantaged racial and socioeconomic backgrounds.

The study received no outside funding. The researchers had no financial conflicts to disclose, but lead author Dr. Goyal is a member of the Pediatrics editorial board. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News editorial advisory board.

SOURCE: Goyal MK et al. Pediatrics. 2020 Sep 24. doi: 10.1542/peds.2020-009951.

Black and Hispanic children comprised significantly more cases of COVID-19, compared with White children, based on data from a large, cross-sectional study of 1,000 cases.

“Data regarding disparities in SARS-CoV-2 infection and outcomes have been, thus far, mostly limited to adults,” wrote Monika K. Goyal, MD, of Children’s National Hospital, Washington, and colleagues. “Additional data further suggest that low socioeconomic status may further exacerbate health outcomes for racial and ethnic minorities.”

In a study published in Pediatrics, the researchers conducted a cross-sectional analysis of 1,000 children from a registry of non–acutely ill pediatric patients seen at a drive-through and walk-up COVID-19 test site.
 

Minority, socioeconomic status affect pediatric outcomes too

Overall, 207 (21%) of the children tested positive for COVID-19; of these 46% were Hispanic, 30% were non-Hispanic Black, and 7% were non-Hispanic White. The median age of the study population was 8 years, and approximately half were male.

The researchers also examined the association of median family income (MFI) using census block group estimates data from the American Community Survey (2014–2018) to represent socioeconomic status.

Infection rates were significantly higher among children in the lowest three quartiles of MFI (24%, 27%, and 38% for quartiles 3, 2, and 1, respectively), compared with the highest quartile of MFI (9%).

After adjusting for age, sex, and MFI, Hispanic children were six times more likely and non-Hispanic Black children were twice as likely to test positive for COVID-19 than non-Hispanic White children (adjusted odds ratios, 6.3 and 2.3, respectively).

The study findings were limited by several factors including the use of clinician-reported ethnicity and thus potential for misclassification, the researchers noted. In addition, the socioeconomic and racial disparities may be underestimated because these groups have less access to primary care, and the study did not allow for confounding variables including housing conditions or occupancy.

“Although it was beyond the scope of this study to understand the causes for these differential rates of infection, the causes may be multifactorial, including, but not limited to, structural factors, poorer access to health care, limited resources, and bias and discrimination,” the researchers noted. In addition, the high infection rate among minority children may be impacted by parents who are less able to telework, find child care, or avoid public transportation, Dr. Goyal and associates wrote.

Future research should address “the modifiable reasons for these observed disparities as well as their differential impact in terms of SARS-CoV-2–related morbidity and mortality outcomes to mitigate the spread of infection and its health effects,” they concluded.
 

How to help

“This study is important because we need to understand which groups of children are at highest risk for SARS-CoV-2 infection in order to maximize efforts for screening, allocating resources, and prioritizing vaccine administration,” Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was not surprised at the higher infection rates in general in minorities and low socioeconomic groups. “We already knew that adult COVID-19 rates were higher for people in certain racial/ethnic groups and those with socioeconomic disadvantages; however, I was shocked by the percentages. That is a huge burden for a population that already has disparities in health outcomes.”

“As the authors cite, this was not a research study of why these groups were more likely to be COVID-19 positive, but they speculated that crowded living conditions, multigenerational families living together, and many minorities being essential workers unable to work from home,” said Dr. Kinsella. Additional factors contributing to higher infection rates may include limited access to care, transportation issues, insurance coverage, schedule challenges, and fear of deportation. Some of these problems might be addressed by coming into communities in mobile vans, visiting community health centers and schools with free educational materials, using masks and hand sanitizer, and offering free access to testing.

“Future studies could confirm the cause of this discrepancy, as well as study community-based interventions and their outcomes,” Dr. Kinsella said. In the meantime, a take-home message for clinicians is the need to prioritize screening, resources, and vaccines to reflect the higher rates of SARS-CoV-2 infections in children from disadvantaged racial and socioeconomic backgrounds.

The study received no outside funding. The researchers had no financial conflicts to disclose, but lead author Dr. Goyal is a member of the Pediatrics editorial board. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News editorial advisory board.

SOURCE: Goyal MK et al. Pediatrics. 2020 Sep 24. doi: 10.1542/peds.2020-009951.