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VNS plus rehab is a powerful poststroke combination
according to preliminary results of a randomized clinical trial at the 2021 annual meeting of the American Academy of Neurology.
“We believe that vagus nerve stimulation combined with rehabilitation is an acceptable and effective intervention for improving upper-limb impairment and function in people with moderate to severe arm weakness a long time VNS-REHAB pivotal study is a randomized, blinded, controlled trial of 108 people who had upper-extremity weakness after having a stroke at least 9 months before enrollment. The average for the group was 3 years post stroke after ischemic stroke,” said Jesse Dawson, MD, a professor at the University of Glasgow.
The Fifty-three patients were assigned active VNS followed by 6 weeks of in-clinic rehabilitation and then 90 days of home-based rehab. At in-clinic rehab, the therapist initiated a 5-second burst of VNS stimulation during each movement. In home-base treatment, the device was activated by a magnet.
Fifty-five patients were assigned sham VNS. After 90 days, the sham group crossed over to receive VNS for 6 weeks and then 90 days of home exercise. This crossover group was the focus of the data Dr. Dawson presented at AAN 2021. The overall trial results have been published in the Lancet.
“The hypothesis is based on the knowledge that the VNS stimulates the release of proneuroplastic neuromodulators norepinephrine and acetylcholine,” Dr. Dawson said. “By pairing VNS with task-specific movement, we hypothesize that we will increase task-specific neuroplasticity.”
The main study showed “a statistically significant difference across all primary and secondary endpoints at all time points in favor of rehabilitation paired with VNS,” Dr. Dawson said. The primary outcome was improvement in Fugl-Meyer Upper Extremity (FMA-UE) outcome, with the active VNS group having a significantly higher percentage of responders. For example, 47% of the active VNS patients had a greater than 6-point response on FMA-UE improvement versus 27% of the sham group (P = .010).
When the sham group crossed over to active VNS, the improvement in arm function matched that of the treatment group in the main study, Dr. Dawson said. “If you look at specifically what happened after they completed the control phase, there was a further small increase in Fugl-Meyer score, but, more importantly between 20% and 35% achieved a clinically important response on the Fugl-Meyer assessment or the Wolf Motor Function Test, giving a number need to treat ranging from three to five,” he said.
Dr. Dawson said that data on adverse events was presented in the Lancet publication. “These were observed at expected frequencies,” he said.
In an interview, he explained the significance of reporting the number to treat. “The number needed to treat helps give an idea of how many times you need to do something to achieve the desired outcome. So for VNS paired with rehab versus rehab alone, you need to treat four people to get one extra clinically important response, compared with just doing therapy.”
The next steps for his group’s research, he said, “will be to try and explore whether we can predict who responds best, and we would like to see if people with other types of stroke benefit.”
In providing comment on the study, Andreas Luft, MD, a professor at the University Hospital Zürich, noted that the FME-UE score improvements reported “are significant and meaningful. ... However, they may also be achieved by increasing the intensity of training. Many medical systems offer their patients high rehabilitation intensities and achieve similar improvements. Whether VNS can further boost higher-intensity training ‘beyond its limits’ is probable but remains to be demonstrated.”
Dr. Luft noted the study advances the knowledge of combining a therapeutic approach with training. “More such approaches are necessary to increase the therapeutic instrumentation of neurorehabilitation,” he said.
Dr. Dawson reported a financial relationship with MicroTransponder. His coauthors reported relationships with MicroTransponder, SanBio, Fujifilm Toyoma Chemical, Medtronic, TRCare, SAEBO, Allergan/AbbVie, Ipsen, Merz, Ottobock/Hangar Orthopedics, Parker Hannifin, Revance Therapeutics, ReWallk, and Sword Health. Three coauthors are employees of MicroTransponder. Dr. Luft has no relevant relationships to disclose.
according to preliminary results of a randomized clinical trial at the 2021 annual meeting of the American Academy of Neurology.
“We believe that vagus nerve stimulation combined with rehabilitation is an acceptable and effective intervention for improving upper-limb impairment and function in people with moderate to severe arm weakness a long time VNS-REHAB pivotal study is a randomized, blinded, controlled trial of 108 people who had upper-extremity weakness after having a stroke at least 9 months before enrollment. The average for the group was 3 years post stroke after ischemic stroke,” said Jesse Dawson, MD, a professor at the University of Glasgow.
The Fifty-three patients were assigned active VNS followed by 6 weeks of in-clinic rehabilitation and then 90 days of home-based rehab. At in-clinic rehab, the therapist initiated a 5-second burst of VNS stimulation during each movement. In home-base treatment, the device was activated by a magnet.
Fifty-five patients were assigned sham VNS. After 90 days, the sham group crossed over to receive VNS for 6 weeks and then 90 days of home exercise. This crossover group was the focus of the data Dr. Dawson presented at AAN 2021. The overall trial results have been published in the Lancet.
“The hypothesis is based on the knowledge that the VNS stimulates the release of proneuroplastic neuromodulators norepinephrine and acetylcholine,” Dr. Dawson said. “By pairing VNS with task-specific movement, we hypothesize that we will increase task-specific neuroplasticity.”
The main study showed “a statistically significant difference across all primary and secondary endpoints at all time points in favor of rehabilitation paired with VNS,” Dr. Dawson said. The primary outcome was improvement in Fugl-Meyer Upper Extremity (FMA-UE) outcome, with the active VNS group having a significantly higher percentage of responders. For example, 47% of the active VNS patients had a greater than 6-point response on FMA-UE improvement versus 27% of the sham group (P = .010).
When the sham group crossed over to active VNS, the improvement in arm function matched that of the treatment group in the main study, Dr. Dawson said. “If you look at specifically what happened after they completed the control phase, there was a further small increase in Fugl-Meyer score, but, more importantly between 20% and 35% achieved a clinically important response on the Fugl-Meyer assessment or the Wolf Motor Function Test, giving a number need to treat ranging from three to five,” he said.
Dr. Dawson said that data on adverse events was presented in the Lancet publication. “These were observed at expected frequencies,” he said.
In an interview, he explained the significance of reporting the number to treat. “The number needed to treat helps give an idea of how many times you need to do something to achieve the desired outcome. So for VNS paired with rehab versus rehab alone, you need to treat four people to get one extra clinically important response, compared with just doing therapy.”
The next steps for his group’s research, he said, “will be to try and explore whether we can predict who responds best, and we would like to see if people with other types of stroke benefit.”
In providing comment on the study, Andreas Luft, MD, a professor at the University Hospital Zürich, noted that the FME-UE score improvements reported “are significant and meaningful. ... However, they may also be achieved by increasing the intensity of training. Many medical systems offer their patients high rehabilitation intensities and achieve similar improvements. Whether VNS can further boost higher-intensity training ‘beyond its limits’ is probable but remains to be demonstrated.”
Dr. Luft noted the study advances the knowledge of combining a therapeutic approach with training. “More such approaches are necessary to increase the therapeutic instrumentation of neurorehabilitation,” he said.
Dr. Dawson reported a financial relationship with MicroTransponder. His coauthors reported relationships with MicroTransponder, SanBio, Fujifilm Toyoma Chemical, Medtronic, TRCare, SAEBO, Allergan/AbbVie, Ipsen, Merz, Ottobock/Hangar Orthopedics, Parker Hannifin, Revance Therapeutics, ReWallk, and Sword Health. Three coauthors are employees of MicroTransponder. Dr. Luft has no relevant relationships to disclose.
according to preliminary results of a randomized clinical trial at the 2021 annual meeting of the American Academy of Neurology.
“We believe that vagus nerve stimulation combined with rehabilitation is an acceptable and effective intervention for improving upper-limb impairment and function in people with moderate to severe arm weakness a long time VNS-REHAB pivotal study is a randomized, blinded, controlled trial of 108 people who had upper-extremity weakness after having a stroke at least 9 months before enrollment. The average for the group was 3 years post stroke after ischemic stroke,” said Jesse Dawson, MD, a professor at the University of Glasgow.
The Fifty-three patients were assigned active VNS followed by 6 weeks of in-clinic rehabilitation and then 90 days of home-based rehab. At in-clinic rehab, the therapist initiated a 5-second burst of VNS stimulation during each movement. In home-base treatment, the device was activated by a magnet.
Fifty-five patients were assigned sham VNS. After 90 days, the sham group crossed over to receive VNS for 6 weeks and then 90 days of home exercise. This crossover group was the focus of the data Dr. Dawson presented at AAN 2021. The overall trial results have been published in the Lancet.
“The hypothesis is based on the knowledge that the VNS stimulates the release of proneuroplastic neuromodulators norepinephrine and acetylcholine,” Dr. Dawson said. “By pairing VNS with task-specific movement, we hypothesize that we will increase task-specific neuroplasticity.”
The main study showed “a statistically significant difference across all primary and secondary endpoints at all time points in favor of rehabilitation paired with VNS,” Dr. Dawson said. The primary outcome was improvement in Fugl-Meyer Upper Extremity (FMA-UE) outcome, with the active VNS group having a significantly higher percentage of responders. For example, 47% of the active VNS patients had a greater than 6-point response on FMA-UE improvement versus 27% of the sham group (P = .010).
When the sham group crossed over to active VNS, the improvement in arm function matched that of the treatment group in the main study, Dr. Dawson said. “If you look at specifically what happened after they completed the control phase, there was a further small increase in Fugl-Meyer score, but, more importantly between 20% and 35% achieved a clinically important response on the Fugl-Meyer assessment or the Wolf Motor Function Test, giving a number need to treat ranging from three to five,” he said.
Dr. Dawson said that data on adverse events was presented in the Lancet publication. “These were observed at expected frequencies,” he said.
In an interview, he explained the significance of reporting the number to treat. “The number needed to treat helps give an idea of how many times you need to do something to achieve the desired outcome. So for VNS paired with rehab versus rehab alone, you need to treat four people to get one extra clinically important response, compared with just doing therapy.”
The next steps for his group’s research, he said, “will be to try and explore whether we can predict who responds best, and we would like to see if people with other types of stroke benefit.”
In providing comment on the study, Andreas Luft, MD, a professor at the University Hospital Zürich, noted that the FME-UE score improvements reported “are significant and meaningful. ... However, they may also be achieved by increasing the intensity of training. Many medical systems offer their patients high rehabilitation intensities and achieve similar improvements. Whether VNS can further boost higher-intensity training ‘beyond its limits’ is probable but remains to be demonstrated.”
Dr. Luft noted the study advances the knowledge of combining a therapeutic approach with training. “More such approaches are necessary to increase the therapeutic instrumentation of neurorehabilitation,” he said.
Dr. Dawson reported a financial relationship with MicroTransponder. His coauthors reported relationships with MicroTransponder, SanBio, Fujifilm Toyoma Chemical, Medtronic, TRCare, SAEBO, Allergan/AbbVie, Ipsen, Merz, Ottobock/Hangar Orthopedics, Parker Hannifin, Revance Therapeutics, ReWallk, and Sword Health. Three coauthors are employees of MicroTransponder. Dr. Luft has no relevant relationships to disclose.
FROM AAN 2021
Are psychiatric disorders a ‘canary in a coal mine’ for Alzheimer’s disease?
, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.
“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”
The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
An inverse correlation between psychiatric disorders and age of Alzheimer’s onset
In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.
“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”
Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.
Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.
“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.
Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.
Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.
“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”
She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
Preliminary and speculative findings
Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”
The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”
He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.
Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.
“Less typical presentations of Alzheimer’s disease, such as posterior cortical atrophy or dysexecutive Alzheimer’s disease, are associated with younger age of onset and are sometimes misdiagnosed as having pure psychiatric disease,” he said. “It is also possible that, in some cases with psychiatric disease, a younger age of onset of cognitive symptoms is charted, even though there are fundamentally two distinct processes at play – a psychiatric disease and a separate neurodegenerative disease – each having independent but additive impacts on cognition.”
Dr. Ramanan added, “This work is also a good reminder to be on the lookout for neuropsychiatric symptoms, treat where indicated, and be open to the possibility that psychiatric symptoms and Alzheimer’s disease can coexist.”
Ms. Eijansantos, Dr. Miller, and Dr. Ramanan have no relevant financial relationships to disclose.
, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.
“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”
The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
An inverse correlation between psychiatric disorders and age of Alzheimer’s onset
In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.
“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”
Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.
Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.
“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.
Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.
Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.
“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”
She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
Preliminary and speculative findings
Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”
The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”
He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.
Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.
“Less typical presentations of Alzheimer’s disease, such as posterior cortical atrophy or dysexecutive Alzheimer’s disease, are associated with younger age of onset and are sometimes misdiagnosed as having pure psychiatric disease,” he said. “It is also possible that, in some cases with psychiatric disease, a younger age of onset of cognitive symptoms is charted, even though there are fundamentally two distinct processes at play – a psychiatric disease and a separate neurodegenerative disease – each having independent but additive impacts on cognition.”
Dr. Ramanan added, “This work is also a good reminder to be on the lookout for neuropsychiatric symptoms, treat where indicated, and be open to the possibility that psychiatric symptoms and Alzheimer’s disease can coexist.”
Ms. Eijansantos, Dr. Miller, and Dr. Ramanan have no relevant financial relationships to disclose.
, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.
“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”
The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
An inverse correlation between psychiatric disorders and age of Alzheimer’s onset
In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.
“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”
Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.
Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.
“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.
Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.
Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.
“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”
She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
Preliminary and speculative findings
Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”
The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”
He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.
Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.
“Less typical presentations of Alzheimer’s disease, such as posterior cortical atrophy or dysexecutive Alzheimer’s disease, are associated with younger age of onset and are sometimes misdiagnosed as having pure psychiatric disease,” he said. “It is also possible that, in some cases with psychiatric disease, a younger age of onset of cognitive symptoms is charted, even though there are fundamentally two distinct processes at play – a psychiatric disease and a separate neurodegenerative disease – each having independent but additive impacts on cognition.”
Dr. Ramanan added, “This work is also a good reminder to be on the lookout for neuropsychiatric symptoms, treat where indicated, and be open to the possibility that psychiatric symptoms and Alzheimer’s disease can coexist.”
Ms. Eijansantos, Dr. Miller, and Dr. Ramanan have no relevant financial relationships to disclose.
FROM AAN 2021
Evobrutinib may lower nerve damage biomarker levels
(MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.
Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.
The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.
Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.
However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.
“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.
In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.
The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”
NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.
“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.
The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.
“However,” he added, “this is a short-term phase 2 trial lacking an active comparator. Inhibitors of BTK have been suggested to have a dual action, acting both in the periphery on the adaptive immune response, but also ameliorating local brain tissue inflammation.”
Additional studies with longer duration, active comparators and advanced neuroimaging will be needed to validate the effect of BTKs on NfL levels in MS, Dr. Piehl said.
The study was sponsored by EMD Serono Research and Development Institute, a Merck affiliate. Dr. Kuhle has no relevant financial relationships to disclose. Dr. Piehl reported financial relationships with Biogen, Novartis, Sanofi, Merck, Actelion, Alexion, Argenx, Roche/Genentech, Genzyme, UCB and Parexel.
(MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.
Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.
The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.
Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.
However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.
“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.
In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.
The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”
NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.
“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.
The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.
“However,” he added, “this is a short-term phase 2 trial lacking an active comparator. Inhibitors of BTK have been suggested to have a dual action, acting both in the periphery on the adaptive immune response, but also ameliorating local brain tissue inflammation.”
Additional studies with longer duration, active comparators and advanced neuroimaging will be needed to validate the effect of BTKs on NfL levels in MS, Dr. Piehl said.
The study was sponsored by EMD Serono Research and Development Institute, a Merck affiliate. Dr. Kuhle has no relevant financial relationships to disclose. Dr. Piehl reported financial relationships with Biogen, Novartis, Sanofi, Merck, Actelion, Alexion, Argenx, Roche/Genentech, Genzyme, UCB and Parexel.
(MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.
Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.
The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.
Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.
However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.
“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.
In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.
The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”
NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.
“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.
The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.
“However,” he added, “this is a short-term phase 2 trial lacking an active comparator. Inhibitors of BTK have been suggested to have a dual action, acting both in the periphery on the adaptive immune response, but also ameliorating local brain tissue inflammation.”
Additional studies with longer duration, active comparators and advanced neuroimaging will be needed to validate the effect of BTKs on NfL levels in MS, Dr. Piehl said.
The study was sponsored by EMD Serono Research and Development Institute, a Merck affiliate. Dr. Kuhle has no relevant financial relationships to disclose. Dr. Piehl reported financial relationships with Biogen, Novartis, Sanofi, Merck, Actelion, Alexion, Argenx, Roche/Genentech, Genzyme, UCB and Parexel.
FROM AAN 2021
Nondopamine antipsychotic shows clinical signal in Parkinson’s disease psychosis
according to results of a proof-of-principle study presented at the 2021 annual meeting of the American Academy of Neurology.
In presenting study results, Stuart H. Isaacson, MD, of the Parkinson’s Disease and Movement Disorders Center in Boca Raton, Fla., noted the one potential advantage of SEP-363856 is that it does not require blood monitoring, unlike clozapine, often used as an alternative to pimavanserin, the only Food and Drug Administration–approved treatment for Parkinson’s disease psychosis.* Quetiapine has also been used off label for Parkinson’s disease psychosis, but Dr. Isaacson said this lacks the evidence supporting the other two options and has side effects including sedation and orthostatic hypotension.
“Other non–FDA-approved treatment options are limited due to their lack of efficacy, safety concerns, and exacerbation of motor symptoms,” he said.
The study involved 38 patients, 24 of whom received SEP-363856 and the rest placebo, and evaluated total scores for the novel Scale for the Assessment of Positive Symptoms for Parkinson’s Disease Psychosis (SAPS-PD) after 6 weeks of treatment. The treatment group was given one of three doses: 25 mg (n = 11), 50 mg (n = 9), and 75 mg (n = 10).
Dr. Isaacson described SEP-363856 as a novel molecule that has agonist activity at TARR1, which regulates dopamine, norepinephrine, and serotonin, as well as serotonin receptor 5-HT1A, but has no activity at the dopamine receptor D2.
“There did appear to be improvement with this medication in patients’ psychosis symptoms, using the SAPS-PD subscale to identify the frequency and severity of hallucinations and delusions, but there was also improvement in the placebo group in this small study,” Dr. Isaacson said. “That did not demonstrate significance.” The improvement was maintained through the study period.
But the gap between the treatment and placebo groups widened as the degree of response increased. The rates were identical for the 30% or above response and the 50% or above response subgroups: 27.3% and 37.5% for placebo and treatment groups, respectively. However, 25% of patients taking SEP-363856 had a 100% response in terms of SAPS-PD score versus 0% in the placebo group, Dr. Isaacson said.
The study also found Mini-Mental State Examination (MMSE) scores improved more in the treatment group, with the gap wider in those with baseline MMSE scores below 24 versus scores above 24: –5.2 (standard deviation, 2.81) versus –2.1 (SD, 3.00; P = .460).
“The scope of daytime and nighttime sleep both showed improvement, with the score for daytime sleep being significant,” Dr. Isaacson said of the treatment group. “Importantly, UPDRS [Unified Parkinson’s Disease Rating Scale] Part III motor scores showed no difference from placebo. Indeed, there was a trend toward improvement, but this again was not significant.” That’s noteworthy, he said, because other antipsychotics, with the exception of clozapine – which requires blood monitoring – are contraindicated in PDP because of their effect on motor function.
During question-and-answer, Dr. Isaacson noted that the complete response rate of 25% with SEP-363856 compared favorably with the 14% complete response rate reported with pimavanserin in the pivotal trial.
“Hopefully greater-powered studies will be performed to further identify and determine the safety and efficacy and tolerably of SEP-363856 in Parkinson’s psychosis, aiming to minimize the placebo effect and to try to hopefully identify its efficacy in relationship to other treatments,” Dr. Isaacson said.
“Right now with only one approved treatment, one that has efficacy but requires blood monitoring, and another treatment that may be fraught sometimes with sleepiness and other side effects, we need other alternatives for our patients as many of them resort to lowering and lowering their dopaminergic therapies with the consequence [of] worsening motor activity,” Dr. Isaacson said.
“This study further supports the concept that Parkinson’s disease psychosis involves much more than simply dopamine,” said Daniel E. Kremens, MD, codirector of the Parkinson’s disease and movement disorders division at Thomas Jefferson University, Philadelphia. “Targeting nondopaminergic targets allows us to treat the psychosis without worsening motor symptoms. By targeting TAAR-1 along with 5HT1A, SEP-363856 is a novel compound that appears to be well tolerated and may treat PDP without worsening motor symptoms,”
Sunovion Pharmaceuticals provided funding for the study. Dr. Isaacson has no financial relationships to disclose. Three study coauthors are employees of Sunovion. Dr. Kremens reported serving as a consultant to Sunovion.
*Correction, 5/17/21: An earlier version of this article misstated the blood monitoring requirements for pimavanserin.
according to results of a proof-of-principle study presented at the 2021 annual meeting of the American Academy of Neurology.
In presenting study results, Stuart H. Isaacson, MD, of the Parkinson’s Disease and Movement Disorders Center in Boca Raton, Fla., noted the one potential advantage of SEP-363856 is that it does not require blood monitoring, unlike clozapine, often used as an alternative to pimavanserin, the only Food and Drug Administration–approved treatment for Parkinson’s disease psychosis.* Quetiapine has also been used off label for Parkinson’s disease psychosis, but Dr. Isaacson said this lacks the evidence supporting the other two options and has side effects including sedation and orthostatic hypotension.
“Other non–FDA-approved treatment options are limited due to their lack of efficacy, safety concerns, and exacerbation of motor symptoms,” he said.
The study involved 38 patients, 24 of whom received SEP-363856 and the rest placebo, and evaluated total scores for the novel Scale for the Assessment of Positive Symptoms for Parkinson’s Disease Psychosis (SAPS-PD) after 6 weeks of treatment. The treatment group was given one of three doses: 25 mg (n = 11), 50 mg (n = 9), and 75 mg (n = 10).
Dr. Isaacson described SEP-363856 as a novel molecule that has agonist activity at TARR1, which regulates dopamine, norepinephrine, and serotonin, as well as serotonin receptor 5-HT1A, but has no activity at the dopamine receptor D2.
“There did appear to be improvement with this medication in patients’ psychosis symptoms, using the SAPS-PD subscale to identify the frequency and severity of hallucinations and delusions, but there was also improvement in the placebo group in this small study,” Dr. Isaacson said. “That did not demonstrate significance.” The improvement was maintained through the study period.
But the gap between the treatment and placebo groups widened as the degree of response increased. The rates were identical for the 30% or above response and the 50% or above response subgroups: 27.3% and 37.5% for placebo and treatment groups, respectively. However, 25% of patients taking SEP-363856 had a 100% response in terms of SAPS-PD score versus 0% in the placebo group, Dr. Isaacson said.
The study also found Mini-Mental State Examination (MMSE) scores improved more in the treatment group, with the gap wider in those with baseline MMSE scores below 24 versus scores above 24: –5.2 (standard deviation, 2.81) versus –2.1 (SD, 3.00; P = .460).
“The scope of daytime and nighttime sleep both showed improvement, with the score for daytime sleep being significant,” Dr. Isaacson said of the treatment group. “Importantly, UPDRS [Unified Parkinson’s Disease Rating Scale] Part III motor scores showed no difference from placebo. Indeed, there was a trend toward improvement, but this again was not significant.” That’s noteworthy, he said, because other antipsychotics, with the exception of clozapine – which requires blood monitoring – are contraindicated in PDP because of their effect on motor function.
During question-and-answer, Dr. Isaacson noted that the complete response rate of 25% with SEP-363856 compared favorably with the 14% complete response rate reported with pimavanserin in the pivotal trial.
“Hopefully greater-powered studies will be performed to further identify and determine the safety and efficacy and tolerably of SEP-363856 in Parkinson’s psychosis, aiming to minimize the placebo effect and to try to hopefully identify its efficacy in relationship to other treatments,” Dr. Isaacson said.
“Right now with only one approved treatment, one that has efficacy but requires blood monitoring, and another treatment that may be fraught sometimes with sleepiness and other side effects, we need other alternatives for our patients as many of them resort to lowering and lowering their dopaminergic therapies with the consequence [of] worsening motor activity,” Dr. Isaacson said.
“This study further supports the concept that Parkinson’s disease psychosis involves much more than simply dopamine,” said Daniel E. Kremens, MD, codirector of the Parkinson’s disease and movement disorders division at Thomas Jefferson University, Philadelphia. “Targeting nondopaminergic targets allows us to treat the psychosis without worsening motor symptoms. By targeting TAAR-1 along with 5HT1A, SEP-363856 is a novel compound that appears to be well tolerated and may treat PDP without worsening motor symptoms,”
Sunovion Pharmaceuticals provided funding for the study. Dr. Isaacson has no financial relationships to disclose. Three study coauthors are employees of Sunovion. Dr. Kremens reported serving as a consultant to Sunovion.
*Correction, 5/17/21: An earlier version of this article misstated the blood monitoring requirements for pimavanserin.
according to results of a proof-of-principle study presented at the 2021 annual meeting of the American Academy of Neurology.
In presenting study results, Stuart H. Isaacson, MD, of the Parkinson’s Disease and Movement Disorders Center in Boca Raton, Fla., noted the one potential advantage of SEP-363856 is that it does not require blood monitoring, unlike clozapine, often used as an alternative to pimavanserin, the only Food and Drug Administration–approved treatment for Parkinson’s disease psychosis.* Quetiapine has also been used off label for Parkinson’s disease psychosis, but Dr. Isaacson said this lacks the evidence supporting the other two options and has side effects including sedation and orthostatic hypotension.
“Other non–FDA-approved treatment options are limited due to their lack of efficacy, safety concerns, and exacerbation of motor symptoms,” he said.
The study involved 38 patients, 24 of whom received SEP-363856 and the rest placebo, and evaluated total scores for the novel Scale for the Assessment of Positive Symptoms for Parkinson’s Disease Psychosis (SAPS-PD) after 6 weeks of treatment. The treatment group was given one of three doses: 25 mg (n = 11), 50 mg (n = 9), and 75 mg (n = 10).
Dr. Isaacson described SEP-363856 as a novel molecule that has agonist activity at TARR1, which regulates dopamine, norepinephrine, and serotonin, as well as serotonin receptor 5-HT1A, but has no activity at the dopamine receptor D2.
“There did appear to be improvement with this medication in patients’ psychosis symptoms, using the SAPS-PD subscale to identify the frequency and severity of hallucinations and delusions, but there was also improvement in the placebo group in this small study,” Dr. Isaacson said. “That did not demonstrate significance.” The improvement was maintained through the study period.
But the gap between the treatment and placebo groups widened as the degree of response increased. The rates were identical for the 30% or above response and the 50% or above response subgroups: 27.3% and 37.5% for placebo and treatment groups, respectively. However, 25% of patients taking SEP-363856 had a 100% response in terms of SAPS-PD score versus 0% in the placebo group, Dr. Isaacson said.
The study also found Mini-Mental State Examination (MMSE) scores improved more in the treatment group, with the gap wider in those with baseline MMSE scores below 24 versus scores above 24: –5.2 (standard deviation, 2.81) versus –2.1 (SD, 3.00; P = .460).
“The scope of daytime and nighttime sleep both showed improvement, with the score for daytime sleep being significant,” Dr. Isaacson said of the treatment group. “Importantly, UPDRS [Unified Parkinson’s Disease Rating Scale] Part III motor scores showed no difference from placebo. Indeed, there was a trend toward improvement, but this again was not significant.” That’s noteworthy, he said, because other antipsychotics, with the exception of clozapine – which requires blood monitoring – are contraindicated in PDP because of their effect on motor function.
During question-and-answer, Dr. Isaacson noted that the complete response rate of 25% with SEP-363856 compared favorably with the 14% complete response rate reported with pimavanserin in the pivotal trial.
“Hopefully greater-powered studies will be performed to further identify and determine the safety and efficacy and tolerably of SEP-363856 in Parkinson’s psychosis, aiming to minimize the placebo effect and to try to hopefully identify its efficacy in relationship to other treatments,” Dr. Isaacson said.
“Right now with only one approved treatment, one that has efficacy but requires blood monitoring, and another treatment that may be fraught sometimes with sleepiness and other side effects, we need other alternatives for our patients as many of them resort to lowering and lowering their dopaminergic therapies with the consequence [of] worsening motor activity,” Dr. Isaacson said.
“This study further supports the concept that Parkinson’s disease psychosis involves much more than simply dopamine,” said Daniel E. Kremens, MD, codirector of the Parkinson’s disease and movement disorders division at Thomas Jefferson University, Philadelphia. “Targeting nondopaminergic targets allows us to treat the psychosis without worsening motor symptoms. By targeting TAAR-1 along with 5HT1A, SEP-363856 is a novel compound that appears to be well tolerated and may treat PDP without worsening motor symptoms,”
Sunovion Pharmaceuticals provided funding for the study. Dr. Isaacson has no financial relationships to disclose. Three study coauthors are employees of Sunovion. Dr. Kremens reported serving as a consultant to Sunovion.
*Correction, 5/17/21: An earlier version of this article misstated the blood monitoring requirements for pimavanserin.
FROM AAN 2021
Investigative gepant liver profile comparable with standard of care
according to results of a multicenter, open-label trial presented at the 2021 annual meeting of the American Academy of Neurology.
The trial included 739 patients, 543 of whom were randomized to daily oral atogepant with the remainder assigned to the existing standard of care oral migraine prevention medication, said Messoud Ashina, MD, PhD, of the Danish Headache Center at the University of Copenhagen. Initially, 67% (n = 364) of the atogepant patients reported treatment-emergent adverse events (TEAEs). However, he noted, the rate of TEAEs related to treatment was actually 18% (n = 98), and the rate of serious AEs was 4.4% (n = 24); 31 patients (5.7%) discontinued therapy because of TEAEs.
Those rates compared favorably with the standard of care group, Dr. Ashina said. In that group, the rate of TEAEs was 78.6% (154/196), and the rate of treatment-related TEAEs was 36.2% (n = 71).
In the atogepant group, the most common TEAEs were upper respiratory tract infection (10.3%, n = 56), constipation (7.2%, n = 39) and nausea (6.3%, n = 34). “With constipation in particular most cases were mild to moderate,” Dr. Ashina said. “Only one case was considered severe and it resolved before the end of the trial.” One patient discontinued treatment because of constipation.
Most significantly, said Dr. Ashina, “No hepatic safety issues were identified.” In the atogepant group, 2.4% of patients (n = 13) had ALT/AST levels at three times the upper limit of normal versus 3.2% (n = 6) in the standard of care group.
During question-and-answer, Dr. Ashina was pressed on the rate or urinary tract infections in the atogepant patients – 5.2% (n = 28), a measure not reported in the standard of care group – but he said there was no indication the UTIs resulted from atogepant itself. “I assume if there was some problems with urinary tract infections because of the kidneys then you would expect to see the lab data showing that,” he added in an interview. “There were no differences in lab abnormalities between the two groups.”
While Dr. Ashina said “I don’t think it’s something of concern” with regard to the UTI risk, he added: “It doesn’t mean that we don’t have to be careful. As physicians, we have to exhibit pharmacovigilance all the time, especially with the new drugs coming out over the next 5 years. But don’t panic.”
Stephen D. Silberstein, MD, director of the headache center at Thomas Jefferson University, Philadelphia, agreed that the hepatic values reported in the open-label trial are important. “What’s really nice about this study is the fact that we now know that this particular gepant when given on a regular basis for 1 year has no problem with liver or kidney function,” he said in an interview.
Dr. Ashina said once-daily oral atogepant could potentially be a desirable alternative migraine preventive treatment to monoclonal antibodies and their quarterly injections and a second-line therapy when other treatments don’t work. However, Dr. Silverstein noted that patients typically aren’t as compliant with self-administered oral medications as they are with periodic injections.
Allergan/AbbVie sponsored the trial. Dr. Ashina reported financial relationships with Allergan/AbbVie, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva. Dr. Silberstein is a trial investigator.
according to results of a multicenter, open-label trial presented at the 2021 annual meeting of the American Academy of Neurology.
The trial included 739 patients, 543 of whom were randomized to daily oral atogepant with the remainder assigned to the existing standard of care oral migraine prevention medication, said Messoud Ashina, MD, PhD, of the Danish Headache Center at the University of Copenhagen. Initially, 67% (n = 364) of the atogepant patients reported treatment-emergent adverse events (TEAEs). However, he noted, the rate of TEAEs related to treatment was actually 18% (n = 98), and the rate of serious AEs was 4.4% (n = 24); 31 patients (5.7%) discontinued therapy because of TEAEs.
Those rates compared favorably with the standard of care group, Dr. Ashina said. In that group, the rate of TEAEs was 78.6% (154/196), and the rate of treatment-related TEAEs was 36.2% (n = 71).
In the atogepant group, the most common TEAEs were upper respiratory tract infection (10.3%, n = 56), constipation (7.2%, n = 39) and nausea (6.3%, n = 34). “With constipation in particular most cases were mild to moderate,” Dr. Ashina said. “Only one case was considered severe and it resolved before the end of the trial.” One patient discontinued treatment because of constipation.
Most significantly, said Dr. Ashina, “No hepatic safety issues were identified.” In the atogepant group, 2.4% of patients (n = 13) had ALT/AST levels at three times the upper limit of normal versus 3.2% (n = 6) in the standard of care group.
During question-and-answer, Dr. Ashina was pressed on the rate or urinary tract infections in the atogepant patients – 5.2% (n = 28), a measure not reported in the standard of care group – but he said there was no indication the UTIs resulted from atogepant itself. “I assume if there was some problems with urinary tract infections because of the kidneys then you would expect to see the lab data showing that,” he added in an interview. “There were no differences in lab abnormalities between the two groups.”
While Dr. Ashina said “I don’t think it’s something of concern” with regard to the UTI risk, he added: “It doesn’t mean that we don’t have to be careful. As physicians, we have to exhibit pharmacovigilance all the time, especially with the new drugs coming out over the next 5 years. But don’t panic.”
Stephen D. Silberstein, MD, director of the headache center at Thomas Jefferson University, Philadelphia, agreed that the hepatic values reported in the open-label trial are important. “What’s really nice about this study is the fact that we now know that this particular gepant when given on a regular basis for 1 year has no problem with liver or kidney function,” he said in an interview.
Dr. Ashina said once-daily oral atogepant could potentially be a desirable alternative migraine preventive treatment to monoclonal antibodies and their quarterly injections and a second-line therapy when other treatments don’t work. However, Dr. Silverstein noted that patients typically aren’t as compliant with self-administered oral medications as they are with periodic injections.
Allergan/AbbVie sponsored the trial. Dr. Ashina reported financial relationships with Allergan/AbbVie, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva. Dr. Silberstein is a trial investigator.
according to results of a multicenter, open-label trial presented at the 2021 annual meeting of the American Academy of Neurology.
The trial included 739 patients, 543 of whom were randomized to daily oral atogepant with the remainder assigned to the existing standard of care oral migraine prevention medication, said Messoud Ashina, MD, PhD, of the Danish Headache Center at the University of Copenhagen. Initially, 67% (n = 364) of the atogepant patients reported treatment-emergent adverse events (TEAEs). However, he noted, the rate of TEAEs related to treatment was actually 18% (n = 98), and the rate of serious AEs was 4.4% (n = 24); 31 patients (5.7%) discontinued therapy because of TEAEs.
Those rates compared favorably with the standard of care group, Dr. Ashina said. In that group, the rate of TEAEs was 78.6% (154/196), and the rate of treatment-related TEAEs was 36.2% (n = 71).
In the atogepant group, the most common TEAEs were upper respiratory tract infection (10.3%, n = 56), constipation (7.2%, n = 39) and nausea (6.3%, n = 34). “With constipation in particular most cases were mild to moderate,” Dr. Ashina said. “Only one case was considered severe and it resolved before the end of the trial.” One patient discontinued treatment because of constipation.
Most significantly, said Dr. Ashina, “No hepatic safety issues were identified.” In the atogepant group, 2.4% of patients (n = 13) had ALT/AST levels at three times the upper limit of normal versus 3.2% (n = 6) in the standard of care group.
During question-and-answer, Dr. Ashina was pressed on the rate or urinary tract infections in the atogepant patients – 5.2% (n = 28), a measure not reported in the standard of care group – but he said there was no indication the UTIs resulted from atogepant itself. “I assume if there was some problems with urinary tract infections because of the kidneys then you would expect to see the lab data showing that,” he added in an interview. “There were no differences in lab abnormalities between the two groups.”
While Dr. Ashina said “I don’t think it’s something of concern” with regard to the UTI risk, he added: “It doesn’t mean that we don’t have to be careful. As physicians, we have to exhibit pharmacovigilance all the time, especially with the new drugs coming out over the next 5 years. But don’t panic.”
Stephen D. Silberstein, MD, director of the headache center at Thomas Jefferson University, Philadelphia, agreed that the hepatic values reported in the open-label trial are important. “What’s really nice about this study is the fact that we now know that this particular gepant when given on a regular basis for 1 year has no problem with liver or kidney function,” he said in an interview.
Dr. Ashina said once-daily oral atogepant could potentially be a desirable alternative migraine preventive treatment to monoclonal antibodies and their quarterly injections and a second-line therapy when other treatments don’t work. However, Dr. Silverstein noted that patients typically aren’t as compliant with self-administered oral medications as they are with periodic injections.
Allergan/AbbVie sponsored the trial. Dr. Ashina reported financial relationships with Allergan/AbbVie, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva. Dr. Silberstein is a trial investigator.
FROM AAN 2021
AHA statement on obesity emphasizes abdominal fat, AFib
An updated American Heart Association scientific statement on the role of obesity in cardiovascular disease provides the first new guidance in 15 years, drawing on evidence that’s emerged in that time to clarify the potential of newer drug therapies and interventions like bariatric surgery and lifestyle modifications to curtail cardiovascular disease risks.
“The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease,” said Tiffany Powell-Wiley, MD, MPH, chair of the volunteer statement writing group.
“One of the big takeaways that I hope people get from the statement is really making it clear that obesity is a complex disease, and that it is multifactorial,” Dr. Powell-Wiley said in an interview. “There are not just biological reasons why individuals have obesity, but there are environmental, psychosocial, and really multilevel factors that contribute to the development and course of obesity.”
Most significantly, Dr. Powell-Wiley said, “we want to emphasize that we really want to have cardiologists think about and focus on abdominal obesity in particular.”
A metric for cardiovascular risk that seems to gain credibility in the statement is the relationship of waist circumference to height regardless of overall weight. “That is a very important finding that we can now really think of waist circumference as an important measure in our clinical practice,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the division of intramural research at the National Heart, Lung, and Blood Institute. “We want to get across to providers that this is something that should be measured and should be followed over time, based on data from the last 15 years that waist circumference and abdominal obesity are associated with higher cardiovascular risk regardless of body mass index.”
The statement provides potentially groundbreaking advice on atrial fibrillation as a consequence of weight, noted Dr. Powell-Wiley. “Up until recently, we haven’t really thought about weight management as a part of managing Afib [atrial fibrillation],” she said. “This statement highlights the need to think about weight management in addition to anticoagulation as part of the pieces for managing Afib.”
Evidence on interventions
The statement, published in Circulation, also dives into the evidence surrounding the varied interventions for managing weight.
“The biggest area where there’s much more data is bariatric surgery,” said Dr. Powell-Wiley. “There’s clear evidence that bariatric surgery lowers cardio mortality and all-cause mortality for patients, but we’ve also seen data around lifestyle interventions, with the Look AHEAD trial, which showed that while there were improvements in CV [cardiovascular] risk factors, we didn’t see the reduction in CV mortality that we wanted to see.”
The statement noted that the Look AHEAD trial (for Action for Health in Diabetes) of people with type 2 diabetes failed to show a significant reduction in major adverse cardiac events or CV mortality after almost 10 years of an intensive weight-loss intervention. Dr. Powell-Wiley added that the result seemed to be related more to the lack of weight loss with lifestyle interventions when compared with bariatric surgery.
The statement also addressed the effectiveness of drug treatments for weight control in managing CV risk, and while the evidence supporting pharmacotherapy specifically for weight loss has been mixed, emerging treatments have shown promise, Dr. Powell-Wiley said. “I think we now have some bright spots with new therapies that have been developed for diabetes and heart failure, such as the SGLT2 inhibitors as well as the GLP-1 agonists, and how they can also appear to improve weight and likely will improve CV mortality in patients with obesity.”
The “obesity paradox,” which Dr. Powell-Wiley noted is “definitely a controversial topic,” is also addressed in the statement. “We try to explain what it is and what we know about it right now,” she said. “We know for instance that patients with obesity, particularly those who have class 1 obesity or patients who are overweight, seem to do better in the short term in relation to coronary artery disease and heart failure, but the reasons for that are not necessarily clear.”
The statement also provides evidence-based insights on the use of diagnostic tools, including stress echocardiography and cardiac MRI as well as coronary angiography, and the clinical significance of specific echocardiographic changes in obese patients.
The writing committee also identified areas that need future research. “It’s really important to emphasize what we learned about the complexity of obesity over this time period,” Dr. Powell-Wiley said. “But again, we don’t have all the answers; there’s a lot more work to be done to understand what type of lifestyle intervention might be most beneficial, especially with addressing abdominal obesity, and how these new therapeutics around heart failure and diabetes may be useful in patients with obesity.
Obesity in adolescents is another area that needs further research, Dr. Powell-Wiley said. “How do we prevent obesity in those populations when we know they’re at risk for so much as they get older? Once you have obesity it’s hard to change that trajectory.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology, the Council on Epidemiology and Prevention, and the Stroke Council. Committee vice chair Paul Poirier, MD, PhD, reported financial relationships with Abbott, Amgen, AstraZeneca, Bausch Health, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi, Servier, and HLS Therapeutics. One committee member disclosed a financial relationship with AstraZeneca. Dr. Powell-Wiley and the other committee members have no relationships to disclose.
An updated American Heart Association scientific statement on the role of obesity in cardiovascular disease provides the first new guidance in 15 years, drawing on evidence that’s emerged in that time to clarify the potential of newer drug therapies and interventions like bariatric surgery and lifestyle modifications to curtail cardiovascular disease risks.
“The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease,” said Tiffany Powell-Wiley, MD, MPH, chair of the volunteer statement writing group.
“One of the big takeaways that I hope people get from the statement is really making it clear that obesity is a complex disease, and that it is multifactorial,” Dr. Powell-Wiley said in an interview. “There are not just biological reasons why individuals have obesity, but there are environmental, psychosocial, and really multilevel factors that contribute to the development and course of obesity.”
Most significantly, Dr. Powell-Wiley said, “we want to emphasize that we really want to have cardiologists think about and focus on abdominal obesity in particular.”
A metric for cardiovascular risk that seems to gain credibility in the statement is the relationship of waist circumference to height regardless of overall weight. “That is a very important finding that we can now really think of waist circumference as an important measure in our clinical practice,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the division of intramural research at the National Heart, Lung, and Blood Institute. “We want to get across to providers that this is something that should be measured and should be followed over time, based on data from the last 15 years that waist circumference and abdominal obesity are associated with higher cardiovascular risk regardless of body mass index.”
The statement provides potentially groundbreaking advice on atrial fibrillation as a consequence of weight, noted Dr. Powell-Wiley. “Up until recently, we haven’t really thought about weight management as a part of managing Afib [atrial fibrillation],” she said. “This statement highlights the need to think about weight management in addition to anticoagulation as part of the pieces for managing Afib.”
Evidence on interventions
The statement, published in Circulation, also dives into the evidence surrounding the varied interventions for managing weight.
“The biggest area where there’s much more data is bariatric surgery,” said Dr. Powell-Wiley. “There’s clear evidence that bariatric surgery lowers cardio mortality and all-cause mortality for patients, but we’ve also seen data around lifestyle interventions, with the Look AHEAD trial, which showed that while there were improvements in CV [cardiovascular] risk factors, we didn’t see the reduction in CV mortality that we wanted to see.”
The statement noted that the Look AHEAD trial (for Action for Health in Diabetes) of people with type 2 diabetes failed to show a significant reduction in major adverse cardiac events or CV mortality after almost 10 years of an intensive weight-loss intervention. Dr. Powell-Wiley added that the result seemed to be related more to the lack of weight loss with lifestyle interventions when compared with bariatric surgery.
The statement also addressed the effectiveness of drug treatments for weight control in managing CV risk, and while the evidence supporting pharmacotherapy specifically for weight loss has been mixed, emerging treatments have shown promise, Dr. Powell-Wiley said. “I think we now have some bright spots with new therapies that have been developed for diabetes and heart failure, such as the SGLT2 inhibitors as well as the GLP-1 agonists, and how they can also appear to improve weight and likely will improve CV mortality in patients with obesity.”
The “obesity paradox,” which Dr. Powell-Wiley noted is “definitely a controversial topic,” is also addressed in the statement. “We try to explain what it is and what we know about it right now,” she said. “We know for instance that patients with obesity, particularly those who have class 1 obesity or patients who are overweight, seem to do better in the short term in relation to coronary artery disease and heart failure, but the reasons for that are not necessarily clear.”
The statement also provides evidence-based insights on the use of diagnostic tools, including stress echocardiography and cardiac MRI as well as coronary angiography, and the clinical significance of specific echocardiographic changes in obese patients.
The writing committee also identified areas that need future research. “It’s really important to emphasize what we learned about the complexity of obesity over this time period,” Dr. Powell-Wiley said. “But again, we don’t have all the answers; there’s a lot more work to be done to understand what type of lifestyle intervention might be most beneficial, especially with addressing abdominal obesity, and how these new therapeutics around heart failure and diabetes may be useful in patients with obesity.
Obesity in adolescents is another area that needs further research, Dr. Powell-Wiley said. “How do we prevent obesity in those populations when we know they’re at risk for so much as they get older? Once you have obesity it’s hard to change that trajectory.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology, the Council on Epidemiology and Prevention, and the Stroke Council. Committee vice chair Paul Poirier, MD, PhD, reported financial relationships with Abbott, Amgen, AstraZeneca, Bausch Health, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi, Servier, and HLS Therapeutics. One committee member disclosed a financial relationship with AstraZeneca. Dr. Powell-Wiley and the other committee members have no relationships to disclose.
An updated American Heart Association scientific statement on the role of obesity in cardiovascular disease provides the first new guidance in 15 years, drawing on evidence that’s emerged in that time to clarify the potential of newer drug therapies and interventions like bariatric surgery and lifestyle modifications to curtail cardiovascular disease risks.
“The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease,” said Tiffany Powell-Wiley, MD, MPH, chair of the volunteer statement writing group.
“One of the big takeaways that I hope people get from the statement is really making it clear that obesity is a complex disease, and that it is multifactorial,” Dr. Powell-Wiley said in an interview. “There are not just biological reasons why individuals have obesity, but there are environmental, psychosocial, and really multilevel factors that contribute to the development and course of obesity.”
Most significantly, Dr. Powell-Wiley said, “we want to emphasize that we really want to have cardiologists think about and focus on abdominal obesity in particular.”
A metric for cardiovascular risk that seems to gain credibility in the statement is the relationship of waist circumference to height regardless of overall weight. “That is a very important finding that we can now really think of waist circumference as an important measure in our clinical practice,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the division of intramural research at the National Heart, Lung, and Blood Institute. “We want to get across to providers that this is something that should be measured and should be followed over time, based on data from the last 15 years that waist circumference and abdominal obesity are associated with higher cardiovascular risk regardless of body mass index.”
The statement provides potentially groundbreaking advice on atrial fibrillation as a consequence of weight, noted Dr. Powell-Wiley. “Up until recently, we haven’t really thought about weight management as a part of managing Afib [atrial fibrillation],” she said. “This statement highlights the need to think about weight management in addition to anticoagulation as part of the pieces for managing Afib.”
Evidence on interventions
The statement, published in Circulation, also dives into the evidence surrounding the varied interventions for managing weight.
“The biggest area where there’s much more data is bariatric surgery,” said Dr. Powell-Wiley. “There’s clear evidence that bariatric surgery lowers cardio mortality and all-cause mortality for patients, but we’ve also seen data around lifestyle interventions, with the Look AHEAD trial, which showed that while there were improvements in CV [cardiovascular] risk factors, we didn’t see the reduction in CV mortality that we wanted to see.”
The statement noted that the Look AHEAD trial (for Action for Health in Diabetes) of people with type 2 diabetes failed to show a significant reduction in major adverse cardiac events or CV mortality after almost 10 years of an intensive weight-loss intervention. Dr. Powell-Wiley added that the result seemed to be related more to the lack of weight loss with lifestyle interventions when compared with bariatric surgery.
The statement also addressed the effectiveness of drug treatments for weight control in managing CV risk, and while the evidence supporting pharmacotherapy specifically for weight loss has been mixed, emerging treatments have shown promise, Dr. Powell-Wiley said. “I think we now have some bright spots with new therapies that have been developed for diabetes and heart failure, such as the SGLT2 inhibitors as well as the GLP-1 agonists, and how they can also appear to improve weight and likely will improve CV mortality in patients with obesity.”
The “obesity paradox,” which Dr. Powell-Wiley noted is “definitely a controversial topic,” is also addressed in the statement. “We try to explain what it is and what we know about it right now,” she said. “We know for instance that patients with obesity, particularly those who have class 1 obesity or patients who are overweight, seem to do better in the short term in relation to coronary artery disease and heart failure, but the reasons for that are not necessarily clear.”
The statement also provides evidence-based insights on the use of diagnostic tools, including stress echocardiography and cardiac MRI as well as coronary angiography, and the clinical significance of specific echocardiographic changes in obese patients.
The writing committee also identified areas that need future research. “It’s really important to emphasize what we learned about the complexity of obesity over this time period,” Dr. Powell-Wiley said. “But again, we don’t have all the answers; there’s a lot more work to be done to understand what type of lifestyle intervention might be most beneficial, especially with addressing abdominal obesity, and how these new therapeutics around heart failure and diabetes may be useful in patients with obesity.
Obesity in adolescents is another area that needs further research, Dr. Powell-Wiley said. “How do we prevent obesity in those populations when we know they’re at risk for so much as they get older? Once you have obesity it’s hard to change that trajectory.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology, the Council on Epidemiology and Prevention, and the Stroke Council. Committee vice chair Paul Poirier, MD, PhD, reported financial relationships with Abbott, Amgen, AstraZeneca, Bausch Health, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi, Servier, and HLS Therapeutics. One committee member disclosed a financial relationship with AstraZeneca. Dr. Powell-Wiley and the other committee members have no relationships to disclose.
FROM CIRCULATION
Study shows how COVID-19 disrupted RA meds
During the first 3 months of the COVID-19 pandemic last year, about one-third of people with rheumatoid arthritis in the United States made changes in their RA medications, and, before the American College of Rheumatology tweaked its guidelines midway through that period, they were about twice as likely to make medication changes on their own than before the pandemic, according to an analysis of data in FORWARD, the National Databank for Rheumatic Diseases.
The study, published in Arthritis Care & Research, also found that about 10% of RA patients on hydroxychloroquine lost access to the drug at a time it was drawing interest as a treatment for COVID-19. Another finding was that a high percentage of patients on non–tumor necrosis factor biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors canceled or postponed appointments.
“Our results show that persons with RA who had medication changes in the first 3 months of the COVID-19 pandemic in the U.S. were more likely to have worse disease activity and higher exposure to prior DMARDs, but no statistical difference was found in terms of comorbidities,” first author Kaleb Michaud, PhD, and coauthors wrote. Dr. Michaud is with the National Databank for Rheumatic Diseases, Wichita, Kan., and the University of Nebraska Medical Center, Omaha.
The study evaluated responses from 734 adults who participated in FORWARD, an observational, multidisease registry. They answered online surveys about COVID-19 in May 2020 and had provided data on their medication use before the pandemic. A total of 30% (n = 221) reported medication changes in that period.
Details on medication changes
Medication changers were more likely to use glucocorticoids (GCs) (32.6% vs. 18.1%) and less likely to use nonhydroxychloroquine conventional DMARDs (49.3% vs. 62%) pre-COVID. Changers also reported higher rates of economic hardship during the pandemic (22.6% vs. 14.6%).
In the midst of the study period, the ACR issued a clinical guideline for treatment of rheumatic and musculoskeletal diseases (RMDs), emphasizing the need to maintain DMARD therapy, control disease activity, and reduce prednisone/GC use. The guideline advised continuing hydroxychloroquine and interleukin-6 inhibitor biologics in people with suspected or confirmed COVID-19.
Dr. Michaud and coauthors acknowledged the ongoing lack of knowledge about real-world treatment patterns for RA during the pandemic. They set out with this study to fill those knowledge gaps.
They noted that patients on bDMARDs (17.6%) and JAK inhibitors (17.1%) were more than twice as likely to discontinue medications than were those on conventional DMARDs (8.2%).
Switching to telehealth was the most common pandemic-related behavior change among patients in all DMARD groups, with rates ranging from 31% to 47.1%, followed by canceling or postponing appointments, with rates ranging from 27.9% to 36.4% depending on the DMARD group.
The study also found that RA patients widely adopted the behavior changes that the Centers for Disease Control and Prevention recommended during the pandemic, although the rates of restricting social contacts were significantly lower than the 90% reported in an early Italian study.
Dr. Michaud and coauthors also provided some explanation of why people on GCs and DMARDs were more likely than others to change medication patterns. “This may reflect efforts to reduce the perceived risk of infections due to GCs as well as the likely less-controlled disease activity associated with GC use,” they wrote. While the ACR’s early pandemic guidance followed the 2015 guidelines – that patients should continue on GCs at the “lowest possible dose” and not stop them “abruptly” – most U.S. rheumatologists reported cutting back on GC use during the pandemic.
The researchers acknowledged that evidence linking GC use with hospitalization for COVID-19, which emerged after they had surveyed study participants, was consistent their findings, but that the overall risk of COVID-19 in RA patients still isn’t known.
Pfizer funded the analysis, and a coauthor is an employee of Pfizer.
During the first 3 months of the COVID-19 pandemic last year, about one-third of people with rheumatoid arthritis in the United States made changes in their RA medications, and, before the American College of Rheumatology tweaked its guidelines midway through that period, they were about twice as likely to make medication changes on their own than before the pandemic, according to an analysis of data in FORWARD, the National Databank for Rheumatic Diseases.
The study, published in Arthritis Care & Research, also found that about 10% of RA patients on hydroxychloroquine lost access to the drug at a time it was drawing interest as a treatment for COVID-19. Another finding was that a high percentage of patients on non–tumor necrosis factor biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors canceled or postponed appointments.
“Our results show that persons with RA who had medication changes in the first 3 months of the COVID-19 pandemic in the U.S. were more likely to have worse disease activity and higher exposure to prior DMARDs, but no statistical difference was found in terms of comorbidities,” first author Kaleb Michaud, PhD, and coauthors wrote. Dr. Michaud is with the National Databank for Rheumatic Diseases, Wichita, Kan., and the University of Nebraska Medical Center, Omaha.
The study evaluated responses from 734 adults who participated in FORWARD, an observational, multidisease registry. They answered online surveys about COVID-19 in May 2020 and had provided data on their medication use before the pandemic. A total of 30% (n = 221) reported medication changes in that period.
Details on medication changes
Medication changers were more likely to use glucocorticoids (GCs) (32.6% vs. 18.1%) and less likely to use nonhydroxychloroquine conventional DMARDs (49.3% vs. 62%) pre-COVID. Changers also reported higher rates of economic hardship during the pandemic (22.6% vs. 14.6%).
In the midst of the study period, the ACR issued a clinical guideline for treatment of rheumatic and musculoskeletal diseases (RMDs), emphasizing the need to maintain DMARD therapy, control disease activity, and reduce prednisone/GC use. The guideline advised continuing hydroxychloroquine and interleukin-6 inhibitor biologics in people with suspected or confirmed COVID-19.
Dr. Michaud and coauthors acknowledged the ongoing lack of knowledge about real-world treatment patterns for RA during the pandemic. They set out with this study to fill those knowledge gaps.
They noted that patients on bDMARDs (17.6%) and JAK inhibitors (17.1%) were more than twice as likely to discontinue medications than were those on conventional DMARDs (8.2%).
Switching to telehealth was the most common pandemic-related behavior change among patients in all DMARD groups, with rates ranging from 31% to 47.1%, followed by canceling or postponing appointments, with rates ranging from 27.9% to 36.4% depending on the DMARD group.
The study also found that RA patients widely adopted the behavior changes that the Centers for Disease Control and Prevention recommended during the pandemic, although the rates of restricting social contacts were significantly lower than the 90% reported in an early Italian study.
Dr. Michaud and coauthors also provided some explanation of why people on GCs and DMARDs were more likely than others to change medication patterns. “This may reflect efforts to reduce the perceived risk of infections due to GCs as well as the likely less-controlled disease activity associated with GC use,” they wrote. While the ACR’s early pandemic guidance followed the 2015 guidelines – that patients should continue on GCs at the “lowest possible dose” and not stop them “abruptly” – most U.S. rheumatologists reported cutting back on GC use during the pandemic.
The researchers acknowledged that evidence linking GC use with hospitalization for COVID-19, which emerged after they had surveyed study participants, was consistent their findings, but that the overall risk of COVID-19 in RA patients still isn’t known.
Pfizer funded the analysis, and a coauthor is an employee of Pfizer.
During the first 3 months of the COVID-19 pandemic last year, about one-third of people with rheumatoid arthritis in the United States made changes in their RA medications, and, before the American College of Rheumatology tweaked its guidelines midway through that period, they were about twice as likely to make medication changes on their own than before the pandemic, according to an analysis of data in FORWARD, the National Databank for Rheumatic Diseases.
The study, published in Arthritis Care & Research, also found that about 10% of RA patients on hydroxychloroquine lost access to the drug at a time it was drawing interest as a treatment for COVID-19. Another finding was that a high percentage of patients on non–tumor necrosis factor biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors canceled or postponed appointments.
“Our results show that persons with RA who had medication changes in the first 3 months of the COVID-19 pandemic in the U.S. were more likely to have worse disease activity and higher exposure to prior DMARDs, but no statistical difference was found in terms of comorbidities,” first author Kaleb Michaud, PhD, and coauthors wrote. Dr. Michaud is with the National Databank for Rheumatic Diseases, Wichita, Kan., and the University of Nebraska Medical Center, Omaha.
The study evaluated responses from 734 adults who participated in FORWARD, an observational, multidisease registry. They answered online surveys about COVID-19 in May 2020 and had provided data on their medication use before the pandemic. A total of 30% (n = 221) reported medication changes in that period.
Details on medication changes
Medication changers were more likely to use glucocorticoids (GCs) (32.6% vs. 18.1%) and less likely to use nonhydroxychloroquine conventional DMARDs (49.3% vs. 62%) pre-COVID. Changers also reported higher rates of economic hardship during the pandemic (22.6% vs. 14.6%).
In the midst of the study period, the ACR issued a clinical guideline for treatment of rheumatic and musculoskeletal diseases (RMDs), emphasizing the need to maintain DMARD therapy, control disease activity, and reduce prednisone/GC use. The guideline advised continuing hydroxychloroquine and interleukin-6 inhibitor biologics in people with suspected or confirmed COVID-19.
Dr. Michaud and coauthors acknowledged the ongoing lack of knowledge about real-world treatment patterns for RA during the pandemic. They set out with this study to fill those knowledge gaps.
They noted that patients on bDMARDs (17.6%) and JAK inhibitors (17.1%) were more than twice as likely to discontinue medications than were those on conventional DMARDs (8.2%).
Switching to telehealth was the most common pandemic-related behavior change among patients in all DMARD groups, with rates ranging from 31% to 47.1%, followed by canceling or postponing appointments, with rates ranging from 27.9% to 36.4% depending on the DMARD group.
The study also found that RA patients widely adopted the behavior changes that the Centers for Disease Control and Prevention recommended during the pandemic, although the rates of restricting social contacts were significantly lower than the 90% reported in an early Italian study.
Dr. Michaud and coauthors also provided some explanation of why people on GCs and DMARDs were more likely than others to change medication patterns. “This may reflect efforts to reduce the perceived risk of infections due to GCs as well as the likely less-controlled disease activity associated with GC use,” they wrote. While the ACR’s early pandemic guidance followed the 2015 guidelines – that patients should continue on GCs at the “lowest possible dose” and not stop them “abruptly” – most U.S. rheumatologists reported cutting back on GC use during the pandemic.
The researchers acknowledged that evidence linking GC use with hospitalization for COVID-19, which emerged after they had surveyed study participants, was consistent their findings, but that the overall risk of COVID-19 in RA patients still isn’t known.
Pfizer funded the analysis, and a coauthor is an employee of Pfizer.
FROM ARTHRITIS CARE & RESEARCH
Study shows potential of remote Parkinson’s disease genotyping
according to a pilot study sponsored by the Parkinson’s Foundation.
“Overall we found high levels of participant satisfaction with Parkinson’s testing and genetic counseling and no significant difference in outcomes concerning satisfaction, knowledge, and impact of genetic testing between disclosure of results and genetic counseling in-person by either a neurologist or a genetic counselor or via telephone by a remove genetic counselor at a centralized center,” said Jennifer L. Verbrugge, MS, a genetic counselor at Indiana University, Indianapolis, in reporting results of the PD GENEration pilot study, presented at the 2021 annual meeting of the American Academy of Neurology.
COVID complication
The study launched in the summer of 2019 with the goal of enrolling 600 participants. However, because of the COVID-19 pandemic, enrollment was truncated. The pilot study eventually enrolled 289 patients, 205 of whom returned their postgenetic counseling surveys, Ms. Verbrugge said. The pilot study goal was to evaluate the feasibility and impact of in-person versus remote genetic testing and counseling for people with Parkinson’s disease.
“The study hopes to reach its ultimate goal, which is to deliver Parkinson’s disease–related genetic testing and counseling to upward of 15,000 people with Parkinson’s,” Ms. Verbrugge said. The program is also planning to expand to include Spanish speakers.
In the pilot study, genetic results were positive in 17% of patients, with 15% (n = 42) having positive heterozygous variants and 8% having variants of uncertain significance. “We did not see significant differences in these outcomes when we compared the mode and genetic counselors involved,” Ms. Verbrugge said.
The study did find that in-person testing and counseling “was associated with increased participant feelings that they were partners in care,” Ms. Verbrugge added. “This is something we are going to continue to evaluate as time goes on.”
However, as the COVID-19 pandemic pushed clinicians to develop virtual platforms, it resulted in a function through which participants can complete all genetic study activities remotely, she said. The study organizers anticipate that as pandemic restrictions ease, they will be able to reach their original goal of 600 participants along with those recruited in an expansion phase.
“As restrictions related to the pandemic ease, we anticipate that more Parkinson’s disease gene-targeted clinical trials will emerge, with aims to recruit people who carry certain gene variants,” Ms. Verbrugge said in an interview. “Many people with Parkinson’s disease may therefore benefit from genetic testing and learning if they carry a Parkinson’s disease related gene variant from participation in the PD GENEration study.”
Increasing patient access
To scale up to the 15,000-population goal for the program, PD GENEration has launched a new protocol designed to increase patient access at new study sites, Ms. Verbrugge said. “This protocol includes an abbreviate version of the clinical data collected, while it maintains the critical component of genetic counseling in the testing process.”
Going forward, the PD GENEration study will focus on improving access to genetic testing and counseling in underrepresented and rural populations, Ms. Verbrugge said. “These efforts will also generate valuable genomic data, allowing researchers to learn more about the causes of Parkinson’s disease in diverse and underrepresented populations. The study will be expanding research efforts concerning the genomic data to gain insights about the seven key genes studied as well as new genes linked to Parkinson’s disease.”
The work of the PD GENEration study is timely, said David K. Simon, MD, PhD, of Harvard Medical School and director of the Parkinson’s Disease & Movement Disorders Center at Beth Israel Deaconess Medical Center, both in Boston. “This is very important to identify such patients now, as clinical trials targeting people with specific genetic mutations or variants are coming soon, and in some cases already are underway. The feasibility and speed of enrollment for those trials will be greatly facilitate if we know in advance who are the people with Parkinson’s disease who have mutations that would make them eligible for the particular trials.”
The fact that the study provides free genetic testing to people with Parkinson’s disease isn’t to be overlooked. “This was an important study to address the question of whether or not remote genetic counseling was feasible and effective, and the results are meaningful given the randomized prospective design,” Dr. Simon said.
Ms. Verbrugge has no relevant relationships to disclose. Dr. Simon reports receiving research funding from the Parkinson’s Foundation.
according to a pilot study sponsored by the Parkinson’s Foundation.
“Overall we found high levels of participant satisfaction with Parkinson’s testing and genetic counseling and no significant difference in outcomes concerning satisfaction, knowledge, and impact of genetic testing between disclosure of results and genetic counseling in-person by either a neurologist or a genetic counselor or via telephone by a remove genetic counselor at a centralized center,” said Jennifer L. Verbrugge, MS, a genetic counselor at Indiana University, Indianapolis, in reporting results of the PD GENEration pilot study, presented at the 2021 annual meeting of the American Academy of Neurology.
COVID complication
The study launched in the summer of 2019 with the goal of enrolling 600 participants. However, because of the COVID-19 pandemic, enrollment was truncated. The pilot study eventually enrolled 289 patients, 205 of whom returned their postgenetic counseling surveys, Ms. Verbrugge said. The pilot study goal was to evaluate the feasibility and impact of in-person versus remote genetic testing and counseling for people with Parkinson’s disease.
“The study hopes to reach its ultimate goal, which is to deliver Parkinson’s disease–related genetic testing and counseling to upward of 15,000 people with Parkinson’s,” Ms. Verbrugge said. The program is also planning to expand to include Spanish speakers.
In the pilot study, genetic results were positive in 17% of patients, with 15% (n = 42) having positive heterozygous variants and 8% having variants of uncertain significance. “We did not see significant differences in these outcomes when we compared the mode and genetic counselors involved,” Ms. Verbrugge said.
The study did find that in-person testing and counseling “was associated with increased participant feelings that they were partners in care,” Ms. Verbrugge added. “This is something we are going to continue to evaluate as time goes on.”
However, as the COVID-19 pandemic pushed clinicians to develop virtual platforms, it resulted in a function through which participants can complete all genetic study activities remotely, she said. The study organizers anticipate that as pandemic restrictions ease, they will be able to reach their original goal of 600 participants along with those recruited in an expansion phase.
“As restrictions related to the pandemic ease, we anticipate that more Parkinson’s disease gene-targeted clinical trials will emerge, with aims to recruit people who carry certain gene variants,” Ms. Verbrugge said in an interview. “Many people with Parkinson’s disease may therefore benefit from genetic testing and learning if they carry a Parkinson’s disease related gene variant from participation in the PD GENEration study.”
Increasing patient access
To scale up to the 15,000-population goal for the program, PD GENEration has launched a new protocol designed to increase patient access at new study sites, Ms. Verbrugge said. “This protocol includes an abbreviate version of the clinical data collected, while it maintains the critical component of genetic counseling in the testing process.”
Going forward, the PD GENEration study will focus on improving access to genetic testing and counseling in underrepresented and rural populations, Ms. Verbrugge said. “These efforts will also generate valuable genomic data, allowing researchers to learn more about the causes of Parkinson’s disease in diverse and underrepresented populations. The study will be expanding research efforts concerning the genomic data to gain insights about the seven key genes studied as well as new genes linked to Parkinson’s disease.”
The work of the PD GENEration study is timely, said David K. Simon, MD, PhD, of Harvard Medical School and director of the Parkinson’s Disease & Movement Disorders Center at Beth Israel Deaconess Medical Center, both in Boston. “This is very important to identify such patients now, as clinical trials targeting people with specific genetic mutations or variants are coming soon, and in some cases already are underway. The feasibility and speed of enrollment for those trials will be greatly facilitate if we know in advance who are the people with Parkinson’s disease who have mutations that would make them eligible for the particular trials.”
The fact that the study provides free genetic testing to people with Parkinson’s disease isn’t to be overlooked. “This was an important study to address the question of whether or not remote genetic counseling was feasible and effective, and the results are meaningful given the randomized prospective design,” Dr. Simon said.
Ms. Verbrugge has no relevant relationships to disclose. Dr. Simon reports receiving research funding from the Parkinson’s Foundation.
according to a pilot study sponsored by the Parkinson’s Foundation.
“Overall we found high levels of participant satisfaction with Parkinson’s testing and genetic counseling and no significant difference in outcomes concerning satisfaction, knowledge, and impact of genetic testing between disclosure of results and genetic counseling in-person by either a neurologist or a genetic counselor or via telephone by a remove genetic counselor at a centralized center,” said Jennifer L. Verbrugge, MS, a genetic counselor at Indiana University, Indianapolis, in reporting results of the PD GENEration pilot study, presented at the 2021 annual meeting of the American Academy of Neurology.
COVID complication
The study launched in the summer of 2019 with the goal of enrolling 600 participants. However, because of the COVID-19 pandemic, enrollment was truncated. The pilot study eventually enrolled 289 patients, 205 of whom returned their postgenetic counseling surveys, Ms. Verbrugge said. The pilot study goal was to evaluate the feasibility and impact of in-person versus remote genetic testing and counseling for people with Parkinson’s disease.
“The study hopes to reach its ultimate goal, which is to deliver Parkinson’s disease–related genetic testing and counseling to upward of 15,000 people with Parkinson’s,” Ms. Verbrugge said. The program is also planning to expand to include Spanish speakers.
In the pilot study, genetic results were positive in 17% of patients, with 15% (n = 42) having positive heterozygous variants and 8% having variants of uncertain significance. “We did not see significant differences in these outcomes when we compared the mode and genetic counselors involved,” Ms. Verbrugge said.
The study did find that in-person testing and counseling “was associated with increased participant feelings that they were partners in care,” Ms. Verbrugge added. “This is something we are going to continue to evaluate as time goes on.”
However, as the COVID-19 pandemic pushed clinicians to develop virtual platforms, it resulted in a function through which participants can complete all genetic study activities remotely, she said. The study organizers anticipate that as pandemic restrictions ease, they will be able to reach their original goal of 600 participants along with those recruited in an expansion phase.
“As restrictions related to the pandemic ease, we anticipate that more Parkinson’s disease gene-targeted clinical trials will emerge, with aims to recruit people who carry certain gene variants,” Ms. Verbrugge said in an interview. “Many people with Parkinson’s disease may therefore benefit from genetic testing and learning if they carry a Parkinson’s disease related gene variant from participation in the PD GENEration study.”
Increasing patient access
To scale up to the 15,000-population goal for the program, PD GENEration has launched a new protocol designed to increase patient access at new study sites, Ms. Verbrugge said. “This protocol includes an abbreviate version of the clinical data collected, while it maintains the critical component of genetic counseling in the testing process.”
Going forward, the PD GENEration study will focus on improving access to genetic testing and counseling in underrepresented and rural populations, Ms. Verbrugge said. “These efforts will also generate valuable genomic data, allowing researchers to learn more about the causes of Parkinson’s disease in diverse and underrepresented populations. The study will be expanding research efforts concerning the genomic data to gain insights about the seven key genes studied as well as new genes linked to Parkinson’s disease.”
The work of the PD GENEration study is timely, said David K. Simon, MD, PhD, of Harvard Medical School and director of the Parkinson’s Disease & Movement Disorders Center at Beth Israel Deaconess Medical Center, both in Boston. “This is very important to identify such patients now, as clinical trials targeting people with specific genetic mutations or variants are coming soon, and in some cases already are underway. The feasibility and speed of enrollment for those trials will be greatly facilitate if we know in advance who are the people with Parkinson’s disease who have mutations that would make them eligible for the particular trials.”
The fact that the study provides free genetic testing to people with Parkinson’s disease isn’t to be overlooked. “This was an important study to address the question of whether or not remote genetic counseling was feasible and effective, and the results are meaningful given the randomized prospective design,” Dr. Simon said.
Ms. Verbrugge has no relevant relationships to disclose. Dr. Simon reports receiving research funding from the Parkinson’s Foundation.
FROM AAN 2021
Pneumonia risk soars in heart failure patients, especially HFpEF
Patients with heart failure get pneumonia at a rate almost three times greater than expected and, once they do get pneumonia, have about a fourfold greater risk of death, investigators for a retrospective analysis of 13,000 patients from two landmark randomized HF trials have found.
The investigators also found that HF patients with preserved ejection fraction (HFpEF) are at the highest risk of developing pneumonia. The findings underscore the importance of patients with HF getting a pneumonia vaccination, they found.
The analysis showed that 6.3% of patients in the PARADIGM-HF trial and 10.6% of those in the PARAGON-HF trial developed pneumonia, reported the study authors, led by John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center at the University of Glasgow in Scotland (J Am Coll Cardiol. 2021;77:1961-73).
“The main reason for doing this study was the fact that many heart failure patients are not vaccinated, as they should be, against pneumonia – both pneumococcus and influenza vaccination,” Dr. McMurray said in an interview. “We wanted to document the frequency and consequences of pneumonia in patients with heart failure to help highlight this deficiency in care.”
Dr. McMurray said he believes this is the first study to document the incidence of pneumonia and pneumonia-related outcomes according to the two major ejection fraction phenotypes.
PARADIGM-HF and PARAGON-HF
The post hoc analysis consisted of 8,399 patients with HF with reduced ejection fraction (HFrEF) in PARADIGM-HF (Eur J Heart Fail. 2013 Sep;15[9]:1062-73) and 4,796 patients with HFpEF in PARAGON-HF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The analysis focused on the 528 and 510 patients in each study, respectively, who developed pneumonia. Those rates translated to an incidence rate of 29 per 1,000 patient-years (95% confidence interval, 27-31) in PARADIGM-HF and 39 per 1,000 patient-years (95% CI, 36-42) in PARAGON-HF.
After pneumonia, the risk of death in patients increased substantially. In PARADIGM-HF, the adjusted hazard ratio for the risk of death from any cause after pneumonia was 4.34 (95% CI, 3.73-5.05). In PARAGON-HF, it was 3.76 (95% CI, 3.09-4.58). HF patients who contracted pneumonia also tended to have HF longer than their counterparts who didn’t develop pneumonia, but the frequency of previous hospitalization for HF didn’t vary between the pneumonia and no-pneumonia groups.
Patients who developed pneumonia tended to be older (average age of 66.9 years vs. 64.6 years, P < .001) and male (83.9% vs. 77.8%, P < .001). The mean age of patients in PARADIGM-HF was almost a decade younger than those in PARAGON-HF, 64 vs. 73 years.
Pneumonia patients also had worse Kansas City Cardiomyopathy Questionnaire scores (76 vs. 80 on average), but no difference in New York Heart Association functional class. “In general, patients who developed pneumonia had more symptoms and signs and HF than those who did not develop pneumonia,” Dr. McMurray and colleagues wrote.
Pneumonia patients also had higher rates of chronic obstructive pulmonary disease (26% vs. 12%), diabetes (43% vs. 34%), and atrial fibrillation (46% vs. 36%).
Another reason for conducting the study, Dr. McMurray said, “was the prior findings in patients with coronary disease and acute myocardial infarction that the risk associated with an episode of pneumonia [e.g., in subsequent vascular events and deaths] persisted long after the acute event. We wanted to see if this was also the case for heart failure, and indeed it was.”
For example, the adjusted HR for cardiovascular death or hospitalization in the first month following an episode of pneumonia was 9.48 (range of 6.85-13.12, P < .001), leveling off to 1.59 after 3 months or more.
Vaccination crucial in HF patients
Dr. McMurray noted that this study emphasizes the importance of pneumonia vaccination for patients with HF. “Given that we have so few treatments to offer patients with HFpEF, this makes the potential value of vaccination in these patients all the greater,” he said.
The COVID-19 pandemic, Dr. McMurray said, is a “good reminder of the dangers of a respiratory infection and the importance of vaccination in these patients. COVID-19 has interesting parallels in being a systemic disease and one with postacute, persisting effects.”
The persistent risk for adverse cardiovascular events 3 months and later after pneumonia is a novel finding of the study, wrote Donna Mancini, MD, and Gregory Gibson, MD, in an invited commentary (J Am Coll Cardiol. 2021;77:1974-6). Both are with the Icahn School of Medicine at Mt. Sinai in New York. The post hoc study also “serves as an important reminder” of pneumonia risk in patients with HF, especially during the pandemic, they wrote.
“Although vaccination alone appears unlikely to be a panacea, it is a readily accessible tool for mitigating disease severity and improving outcomes,” Dr. Mancini and Dr. Gibson wrote. “After all, an ounce of prevention is worth a pound of cure.”
Novartis provided funding for the PARADIGM-HF and PARAGON-HF trials, and Dr. McMurray and coauthors disclosed financial relationships with Novartis. Dr. Mancini and Dr. Gibson have no relevant financial relationships to disclose.
Patients with heart failure get pneumonia at a rate almost three times greater than expected and, once they do get pneumonia, have about a fourfold greater risk of death, investigators for a retrospective analysis of 13,000 patients from two landmark randomized HF trials have found.
The investigators also found that HF patients with preserved ejection fraction (HFpEF) are at the highest risk of developing pneumonia. The findings underscore the importance of patients with HF getting a pneumonia vaccination, they found.
The analysis showed that 6.3% of patients in the PARADIGM-HF trial and 10.6% of those in the PARAGON-HF trial developed pneumonia, reported the study authors, led by John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center at the University of Glasgow in Scotland (J Am Coll Cardiol. 2021;77:1961-73).
“The main reason for doing this study was the fact that many heart failure patients are not vaccinated, as they should be, against pneumonia – both pneumococcus and influenza vaccination,” Dr. McMurray said in an interview. “We wanted to document the frequency and consequences of pneumonia in patients with heart failure to help highlight this deficiency in care.”
Dr. McMurray said he believes this is the first study to document the incidence of pneumonia and pneumonia-related outcomes according to the two major ejection fraction phenotypes.
PARADIGM-HF and PARAGON-HF
The post hoc analysis consisted of 8,399 patients with HF with reduced ejection fraction (HFrEF) in PARADIGM-HF (Eur J Heart Fail. 2013 Sep;15[9]:1062-73) and 4,796 patients with HFpEF in PARAGON-HF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The analysis focused on the 528 and 510 patients in each study, respectively, who developed pneumonia. Those rates translated to an incidence rate of 29 per 1,000 patient-years (95% confidence interval, 27-31) in PARADIGM-HF and 39 per 1,000 patient-years (95% CI, 36-42) in PARAGON-HF.
After pneumonia, the risk of death in patients increased substantially. In PARADIGM-HF, the adjusted hazard ratio for the risk of death from any cause after pneumonia was 4.34 (95% CI, 3.73-5.05). In PARAGON-HF, it was 3.76 (95% CI, 3.09-4.58). HF patients who contracted pneumonia also tended to have HF longer than their counterparts who didn’t develop pneumonia, but the frequency of previous hospitalization for HF didn’t vary between the pneumonia and no-pneumonia groups.
Patients who developed pneumonia tended to be older (average age of 66.9 years vs. 64.6 years, P < .001) and male (83.9% vs. 77.8%, P < .001). The mean age of patients in PARADIGM-HF was almost a decade younger than those in PARAGON-HF, 64 vs. 73 years.
Pneumonia patients also had worse Kansas City Cardiomyopathy Questionnaire scores (76 vs. 80 on average), but no difference in New York Heart Association functional class. “In general, patients who developed pneumonia had more symptoms and signs and HF than those who did not develop pneumonia,” Dr. McMurray and colleagues wrote.
Pneumonia patients also had higher rates of chronic obstructive pulmonary disease (26% vs. 12%), diabetes (43% vs. 34%), and atrial fibrillation (46% vs. 36%).
Another reason for conducting the study, Dr. McMurray said, “was the prior findings in patients with coronary disease and acute myocardial infarction that the risk associated with an episode of pneumonia [e.g., in subsequent vascular events and deaths] persisted long after the acute event. We wanted to see if this was also the case for heart failure, and indeed it was.”
For example, the adjusted HR for cardiovascular death or hospitalization in the first month following an episode of pneumonia was 9.48 (range of 6.85-13.12, P < .001), leveling off to 1.59 after 3 months or more.
Vaccination crucial in HF patients
Dr. McMurray noted that this study emphasizes the importance of pneumonia vaccination for patients with HF. “Given that we have so few treatments to offer patients with HFpEF, this makes the potential value of vaccination in these patients all the greater,” he said.
The COVID-19 pandemic, Dr. McMurray said, is a “good reminder of the dangers of a respiratory infection and the importance of vaccination in these patients. COVID-19 has interesting parallels in being a systemic disease and one with postacute, persisting effects.”
The persistent risk for adverse cardiovascular events 3 months and later after pneumonia is a novel finding of the study, wrote Donna Mancini, MD, and Gregory Gibson, MD, in an invited commentary (J Am Coll Cardiol. 2021;77:1974-6). Both are with the Icahn School of Medicine at Mt. Sinai in New York. The post hoc study also “serves as an important reminder” of pneumonia risk in patients with HF, especially during the pandemic, they wrote.
“Although vaccination alone appears unlikely to be a panacea, it is a readily accessible tool for mitigating disease severity and improving outcomes,” Dr. Mancini and Dr. Gibson wrote. “After all, an ounce of prevention is worth a pound of cure.”
Novartis provided funding for the PARADIGM-HF and PARAGON-HF trials, and Dr. McMurray and coauthors disclosed financial relationships with Novartis. Dr. Mancini and Dr. Gibson have no relevant financial relationships to disclose.
Patients with heart failure get pneumonia at a rate almost three times greater than expected and, once they do get pneumonia, have about a fourfold greater risk of death, investigators for a retrospective analysis of 13,000 patients from two landmark randomized HF trials have found.
The investigators also found that HF patients with preserved ejection fraction (HFpEF) are at the highest risk of developing pneumonia. The findings underscore the importance of patients with HF getting a pneumonia vaccination, they found.
The analysis showed that 6.3% of patients in the PARADIGM-HF trial and 10.6% of those in the PARAGON-HF trial developed pneumonia, reported the study authors, led by John J.V. McMurray, MD, of the British Heart Foundation Cardiovascular Research Center at the University of Glasgow in Scotland (J Am Coll Cardiol. 2021;77:1961-73).
“The main reason for doing this study was the fact that many heart failure patients are not vaccinated, as they should be, against pneumonia – both pneumococcus and influenza vaccination,” Dr. McMurray said in an interview. “We wanted to document the frequency and consequences of pneumonia in patients with heart failure to help highlight this deficiency in care.”
Dr. McMurray said he believes this is the first study to document the incidence of pneumonia and pneumonia-related outcomes according to the two major ejection fraction phenotypes.
PARADIGM-HF and PARAGON-HF
The post hoc analysis consisted of 8,399 patients with HF with reduced ejection fraction (HFrEF) in PARADIGM-HF (Eur J Heart Fail. 2013 Sep;15[9]:1062-73) and 4,796 patients with HFpEF in PARAGON-HF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). The analysis focused on the 528 and 510 patients in each study, respectively, who developed pneumonia. Those rates translated to an incidence rate of 29 per 1,000 patient-years (95% confidence interval, 27-31) in PARADIGM-HF and 39 per 1,000 patient-years (95% CI, 36-42) in PARAGON-HF.
After pneumonia, the risk of death in patients increased substantially. In PARADIGM-HF, the adjusted hazard ratio for the risk of death from any cause after pneumonia was 4.34 (95% CI, 3.73-5.05). In PARAGON-HF, it was 3.76 (95% CI, 3.09-4.58). HF patients who contracted pneumonia also tended to have HF longer than their counterparts who didn’t develop pneumonia, but the frequency of previous hospitalization for HF didn’t vary between the pneumonia and no-pneumonia groups.
Patients who developed pneumonia tended to be older (average age of 66.9 years vs. 64.6 years, P < .001) and male (83.9% vs. 77.8%, P < .001). The mean age of patients in PARADIGM-HF was almost a decade younger than those in PARAGON-HF, 64 vs. 73 years.
Pneumonia patients also had worse Kansas City Cardiomyopathy Questionnaire scores (76 vs. 80 on average), but no difference in New York Heart Association functional class. “In general, patients who developed pneumonia had more symptoms and signs and HF than those who did not develop pneumonia,” Dr. McMurray and colleagues wrote.
Pneumonia patients also had higher rates of chronic obstructive pulmonary disease (26% vs. 12%), diabetes (43% vs. 34%), and atrial fibrillation (46% vs. 36%).
Another reason for conducting the study, Dr. McMurray said, “was the prior findings in patients with coronary disease and acute myocardial infarction that the risk associated with an episode of pneumonia [e.g., in subsequent vascular events and deaths] persisted long after the acute event. We wanted to see if this was also the case for heart failure, and indeed it was.”
For example, the adjusted HR for cardiovascular death or hospitalization in the first month following an episode of pneumonia was 9.48 (range of 6.85-13.12, P < .001), leveling off to 1.59 after 3 months or more.
Vaccination crucial in HF patients
Dr. McMurray noted that this study emphasizes the importance of pneumonia vaccination for patients with HF. “Given that we have so few treatments to offer patients with HFpEF, this makes the potential value of vaccination in these patients all the greater,” he said.
The COVID-19 pandemic, Dr. McMurray said, is a “good reminder of the dangers of a respiratory infection and the importance of vaccination in these patients. COVID-19 has interesting parallels in being a systemic disease and one with postacute, persisting effects.”
The persistent risk for adverse cardiovascular events 3 months and later after pneumonia is a novel finding of the study, wrote Donna Mancini, MD, and Gregory Gibson, MD, in an invited commentary (J Am Coll Cardiol. 2021;77:1974-6). Both are with the Icahn School of Medicine at Mt. Sinai in New York. The post hoc study also “serves as an important reminder” of pneumonia risk in patients with HF, especially during the pandemic, they wrote.
“Although vaccination alone appears unlikely to be a panacea, it is a readily accessible tool for mitigating disease severity and improving outcomes,” Dr. Mancini and Dr. Gibson wrote. “After all, an ounce of prevention is worth a pound of cure.”
Novartis provided funding for the PARADIGM-HF and PARAGON-HF trials, and Dr. McMurray and coauthors disclosed financial relationships with Novartis. Dr. Mancini and Dr. Gibson have no relevant financial relationships to disclose.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
The best exercises for BP control? European statement sorts it out
Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.
Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.
The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.
The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).
By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.
“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”
Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).
The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.
The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:
- Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
- High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
- Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.
They note that more research is needed to validate the BP-lowering effects of combined exercise.
The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.
Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.
“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”
The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.
“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”
Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.
Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.
Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.
The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.
The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).
By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.
“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”
Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).
The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.
The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:
- Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
- High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
- Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.
They note that more research is needed to validate the BP-lowering effects of combined exercise.
The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.
Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.
“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”
The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.
“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”
Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.
Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.
Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.
The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.
The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).
By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.
“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”
Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).
The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.
The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:
- Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
- High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
- Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.
They note that more research is needed to validate the BP-lowering effects of combined exercise.
The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.
Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.
“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”
The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.
“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”
Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.
FROM THE EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY