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AI interpretation of CCTA unlocks value of inflammation as CV risk factor
Risk calculations might be transformed
, according to a study that suggests this approach would change treatment about half the time.
In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.
This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.
Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
CCTA-based inflammation is promising
The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.
So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.
In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).
The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.
When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.
The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.
“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
Predictive value greater in nonobstructive CAD
When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.
When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.
When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.
When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.
Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.
“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
Imaging has potential for expanded risk assessment
The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.
“A registry is not a randomized trial,” she said.
Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.
Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.
“This is an incredibly intriguing idea that deserves continuing research,” she said.
Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.
Risk calculations might be transformed
Risk calculations might be transformed
, according to a study that suggests this approach would change treatment about half the time.
In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.
This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.
Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
CCTA-based inflammation is promising
The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.
So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.
In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).
The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.
When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.
The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.
“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
Predictive value greater in nonobstructive CAD
When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.
When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.
When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.
When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.
Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.
“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
Imaging has potential for expanded risk assessment
The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.
“A registry is not a randomized trial,” she said.
Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.
Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.
“This is an incredibly intriguing idea that deserves continuing research,” she said.
Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.
, according to a study that suggests this approach would change treatment about half the time.
In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.
This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.
Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
CCTA-based inflammation is promising
The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.
So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.
In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).
The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.
When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.
The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.
“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
Predictive value greater in nonobstructive CAD
When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.
When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.
When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.
When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.
Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.
“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
Imaging has potential for expanded risk assessment
The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.
“A registry is not a randomized trial,” she said.
Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.
Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.
“This is an incredibly intriguing idea that deserves continuing research,” she said.
Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.
FROM AHA 2023
Parent concerns a factor when treating eczema in children with darker skin types
NEW YORK –
Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.
“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.
In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
Consider the parent’s perspective
“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.
For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.
As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.
“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
Pigmentary changes are a priority
However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.
“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.
“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.
Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.
In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”
Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.
She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.
Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.
“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
Restoring skin tone can be the priority
Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”
“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.
Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.
“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.
Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.
NEW YORK –
Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.
“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.
In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
Consider the parent’s perspective
“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.
For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.
As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.
“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
Pigmentary changes are a priority
However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.
“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.
“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.
Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.
In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”
Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.
She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.
Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.
“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
Restoring skin tone can be the priority
Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”
“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.
Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.
“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.
Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.
NEW YORK –
Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.
“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.
In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
Consider the parent’s perspective
“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.
For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.
As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.
“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
Pigmentary changes are a priority
However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.
“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.
“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.
Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.
In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”
Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.
She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.
Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.
“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
Restoring skin tone can be the priority
Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”
“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.
Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.
“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.
Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.
AT SOC 2023
Adolescents with migraine need smooth handoff to adult care
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Alternative antirejection regimen is efficacious in pediatric heart transplant
Study challenges everolimus boxed warning
according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.
Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.
Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.
In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
Everolimus- vs. MMF-based antirejection
The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m2 every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).
In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).
The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).
Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
Numerical advantage for everolimus on efficacy
The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.
Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.
On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.
In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).
Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).
Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
Study supports safety of everolimus regimen
The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.
However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.
“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.
Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.
He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.
Early mortality based on infection “was not observed in our study,” he said.
The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.
Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,
Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.
Study challenges everolimus boxed warning
Study challenges everolimus boxed warning
according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.
Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.
Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.
In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
Everolimus- vs. MMF-based antirejection
The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m2 every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).
In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).
The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).
Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
Numerical advantage for everolimus on efficacy
The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.
Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.
On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.
In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).
Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).
Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
Study supports safety of everolimus regimen
The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.
However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.
“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.
Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.
He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.
Early mortality based on infection “was not observed in our study,” he said.
The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.
Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,
Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.
according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.
Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.
Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.
In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
Everolimus- vs. MMF-based antirejection
The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m2 every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).
In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).
The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).
Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
Numerical advantage for everolimus on efficacy
The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.
Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.
On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.
In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).
Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).
Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
Study supports safety of everolimus regimen
The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.
However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.
“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.
Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.
He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.
Early mortality based on infection “was not observed in our study,” he said.
The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.
Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,
Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.
FROM AHA 2023
Avoid adding to minority stress when treating headache in LGBTQIA+ patients
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Pharmacist-based strategy places more patients on statins
Visit-based strategy has more modest effect
PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.
, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.
The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.
The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
EHR algorithm identifies statin candidates
The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.
Dr. Faranoff described these interventions as non–visit related and visit related.
In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.
In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.
During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).
In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
Visit-based study also randomized
In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,
More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.
For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.
For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).
In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,
The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.
Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
Overcoming clinical inertia a challenge
The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.
Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.
“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”
This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.
Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.
Visit-based strategy has more modest effect
Visit-based strategy has more modest effect
PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.
, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.
The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.
The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
EHR algorithm identifies statin candidates
The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.
Dr. Faranoff described these interventions as non–visit related and visit related.
In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.
In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.
During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).
In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
Visit-based study also randomized
In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,
More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.
For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.
For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).
In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,
The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.
Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
Overcoming clinical inertia a challenge
The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.
Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.
“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”
This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.
Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.
PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.
, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.
The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.
The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
EHR algorithm identifies statin candidates
The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.
Dr. Faranoff described these interventions as non–visit related and visit related.
In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.
In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.
During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).
In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
Visit-based study also randomized
In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,
More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.
For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.
For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).
In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,
The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.
Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
Overcoming clinical inertia a challenge
The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.
Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.
“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”
This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.
Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.
AT AHA 2023
For AFib cardioversion in obesity, dual energy might be the answer
PHILADELPHIA – , a multicenter randomized trial shows.
When treated with dual direct current cardioversion (DCCV), only 2% of patients with obesity failed to cardiovert on the first shock versus 14% (P = .002) of those treated with a conventional single DCCV, reported Joshua D. Aymond, MD, a fellow in electrophysiology at Ochsner Health, New Orleans.
Of the 14 patients in the single DCCV arm who did not convert on the first shock, 12 cardioverted when switched to dual energy. The remaining two cardioverted on the second dual shock.
In the dual DCCV group, of the two patients who did not cardiovert on the first dual shock, one did on the second. The other also cardioverted on a second shock, but this second shock was not delivered for 2 weeks, during which time the patient received a course of amiodarone-based anti-arrhythmic therapy.
No disadvantages seen with dual energy
The greater efficacy of a first shock with dual DCCV was achieved with no apparent disadvantages. There were no differences in post-procedure chest discomfort and no procedure-related adverse events in either arm, Dr. Aymond said.
The rising prevalence of obesity in the United States has created the need for a more effective first-line strategy for AF, noted Dr. Aymond, who presented the results of this study at the annual scientific sessions of the American Heart Association.
Cardioversion, which he characterized as the treatment of choice for AF, “fails to restore sinus rhythm in 20% to 35% of obese patients versus less than 10% of non-obese patients,” he said. The higher failure rate in patients with obesity is becoming a more common clinical issue not only due to the rising rates of obesity but a corresponding rise in AF, which is a related phenomenon.
“The risk of atrial fibrillation is increased by 50% relative to those who are not obese,” Dr. Aymond explained.
In this study, 200 patients at three participating centers were randomized to single DCCV or double DCCV after exclusions that included ventricular tachycardia and respiratory instability. The baseline characteristics were comparable. All 101 patients in the single DCCV group and 99 patients in the dual DCCV group were available for the intention-to-treat analysis.
200 vs. 400 joules delivered across the heart
In the study protocol, patients were fitted with four chest pads, two located adjacent but above the heart and two adjacent but below the heart. For single DCCV, 200 joules of energy were delivered from the upper right pad to the lower left pad across the heart. For dual DCCV, another 200 joules were delivered simultaneously from the upper left to the lower right across the heart. The total dose in the dual DCCV group was 400 joules.
The primary outcome was restoration of sinus rhythm of any duration immediately after DCCV. Safety, including clinical events, was a secondary outcome. Only the patients were blinded to the energy they received.
On univariate analysis, the odds ratio for successful cardioversion with dual DCCV was nearly eightfold higher (OR 7.8; P = .008) than single DCCV. On a simple multivariable analysis, when the researchers controlled for just age, sex, and body mass index, the odds ratio rose (OR 8.5; P = .007).
On a comprehensive multivariable analysis adding control for such characteristics as left ventricular ejection fraction (LVEF), obstructive sleep apnea, and antiarrhythmic drugs, the advantage of dual DCCV climbed above 12-fold (OR 12.6; P = .03).
The study is addressing a relevant and persistent question, said the AHA-invited discussant Jose A. Joglar, MD, program director, Clinical Cardiac Electrophysiology Fellowship, University of Texas Southwestern Medical Center, Dallas.
Dr. Joglar pointed out that alternatives to single DCCV for patients more difficult to cardiovert have been “sought for decades.” He noted that a variety of techniques, including dual DCCV, have been evaluated in small studies and case reports.
Alternatives for obese outlined
Several have shown promise, Dr. Joglar said. As one of several examples, he cited a 20-patient study that randomized patients to adhesive patches, like those employed in the Aymond trial, or handheld paddles. Both patches and paddles were applied with manual pressure while a 200-joule shock was delivered. The proportion of patients who cardioverted on the first shock was almost two times higher in the group after the first shock with the paddles (50% vs. 27%; P = .01). Dr. Joglar said the study supports the principle that 200 joules delivered by adhesive patches is inadequate for treatment of AF in many patients with obesity.
Dr. Joglar also cited studies suggesting that single DCCV delivered with higher energy than 200 joules appears to improve cardioversion success rates, but he indicated that this study with dual DCCV in the front-line setting provides evidence for another alternative.
“This is the first such trial with dual defibrillators as an initial strategy,” he said, calling the groups well matched and the superiority of dual DCCV “impressive.” He cautioned that the study size was well powered for the endpoint but perhaps small for evaluating relative safety.
Yet, “the study adds credibility and confidence for the use of dual DCCV, especially in difficult or refractory patients,” he said. He is less certain that it establishes dual DCCV as a standard first-line therapy in all patients with obesity. This would require additional studies to compare it to other types of strategies such as those he mentioned.
As an option for improving cardioversion in first-line treatment, dual DCCV “can be added to a list of other techniques, such as manual pressure or a higher initial dose with single DCCV,” he said.
Dr. Aymond and Dr. Joglar report no potential conflicts of interest.
PHILADELPHIA – , a multicenter randomized trial shows.
When treated with dual direct current cardioversion (DCCV), only 2% of patients with obesity failed to cardiovert on the first shock versus 14% (P = .002) of those treated with a conventional single DCCV, reported Joshua D. Aymond, MD, a fellow in electrophysiology at Ochsner Health, New Orleans.
Of the 14 patients in the single DCCV arm who did not convert on the first shock, 12 cardioverted when switched to dual energy. The remaining two cardioverted on the second dual shock.
In the dual DCCV group, of the two patients who did not cardiovert on the first dual shock, one did on the second. The other also cardioverted on a second shock, but this second shock was not delivered for 2 weeks, during which time the patient received a course of amiodarone-based anti-arrhythmic therapy.
No disadvantages seen with dual energy
The greater efficacy of a first shock with dual DCCV was achieved with no apparent disadvantages. There were no differences in post-procedure chest discomfort and no procedure-related adverse events in either arm, Dr. Aymond said.
The rising prevalence of obesity in the United States has created the need for a more effective first-line strategy for AF, noted Dr. Aymond, who presented the results of this study at the annual scientific sessions of the American Heart Association.
Cardioversion, which he characterized as the treatment of choice for AF, “fails to restore sinus rhythm in 20% to 35% of obese patients versus less than 10% of non-obese patients,” he said. The higher failure rate in patients with obesity is becoming a more common clinical issue not only due to the rising rates of obesity but a corresponding rise in AF, which is a related phenomenon.
“The risk of atrial fibrillation is increased by 50% relative to those who are not obese,” Dr. Aymond explained.
In this study, 200 patients at three participating centers were randomized to single DCCV or double DCCV after exclusions that included ventricular tachycardia and respiratory instability. The baseline characteristics were comparable. All 101 patients in the single DCCV group and 99 patients in the dual DCCV group were available for the intention-to-treat analysis.
200 vs. 400 joules delivered across the heart
In the study protocol, patients were fitted with four chest pads, two located adjacent but above the heart and two adjacent but below the heart. For single DCCV, 200 joules of energy were delivered from the upper right pad to the lower left pad across the heart. For dual DCCV, another 200 joules were delivered simultaneously from the upper left to the lower right across the heart. The total dose in the dual DCCV group was 400 joules.
The primary outcome was restoration of sinus rhythm of any duration immediately after DCCV. Safety, including clinical events, was a secondary outcome. Only the patients were blinded to the energy they received.
On univariate analysis, the odds ratio for successful cardioversion with dual DCCV was nearly eightfold higher (OR 7.8; P = .008) than single DCCV. On a simple multivariable analysis, when the researchers controlled for just age, sex, and body mass index, the odds ratio rose (OR 8.5; P = .007).
On a comprehensive multivariable analysis adding control for such characteristics as left ventricular ejection fraction (LVEF), obstructive sleep apnea, and antiarrhythmic drugs, the advantage of dual DCCV climbed above 12-fold (OR 12.6; P = .03).
The study is addressing a relevant and persistent question, said the AHA-invited discussant Jose A. Joglar, MD, program director, Clinical Cardiac Electrophysiology Fellowship, University of Texas Southwestern Medical Center, Dallas.
Dr. Joglar pointed out that alternatives to single DCCV for patients more difficult to cardiovert have been “sought for decades.” He noted that a variety of techniques, including dual DCCV, have been evaluated in small studies and case reports.
Alternatives for obese outlined
Several have shown promise, Dr. Joglar said. As one of several examples, he cited a 20-patient study that randomized patients to adhesive patches, like those employed in the Aymond trial, or handheld paddles. Both patches and paddles were applied with manual pressure while a 200-joule shock was delivered. The proportion of patients who cardioverted on the first shock was almost two times higher in the group after the first shock with the paddles (50% vs. 27%; P = .01). Dr. Joglar said the study supports the principle that 200 joules delivered by adhesive patches is inadequate for treatment of AF in many patients with obesity.
Dr. Joglar also cited studies suggesting that single DCCV delivered with higher energy than 200 joules appears to improve cardioversion success rates, but he indicated that this study with dual DCCV in the front-line setting provides evidence for another alternative.
“This is the first such trial with dual defibrillators as an initial strategy,” he said, calling the groups well matched and the superiority of dual DCCV “impressive.” He cautioned that the study size was well powered for the endpoint but perhaps small for evaluating relative safety.
Yet, “the study adds credibility and confidence for the use of dual DCCV, especially in difficult or refractory patients,” he said. He is less certain that it establishes dual DCCV as a standard first-line therapy in all patients with obesity. This would require additional studies to compare it to other types of strategies such as those he mentioned.
As an option for improving cardioversion in first-line treatment, dual DCCV “can be added to a list of other techniques, such as manual pressure or a higher initial dose with single DCCV,” he said.
Dr. Aymond and Dr. Joglar report no potential conflicts of interest.
PHILADELPHIA – , a multicenter randomized trial shows.
When treated with dual direct current cardioversion (DCCV), only 2% of patients with obesity failed to cardiovert on the first shock versus 14% (P = .002) of those treated with a conventional single DCCV, reported Joshua D. Aymond, MD, a fellow in electrophysiology at Ochsner Health, New Orleans.
Of the 14 patients in the single DCCV arm who did not convert on the first shock, 12 cardioverted when switched to dual energy. The remaining two cardioverted on the second dual shock.
In the dual DCCV group, of the two patients who did not cardiovert on the first dual shock, one did on the second. The other also cardioverted on a second shock, but this second shock was not delivered for 2 weeks, during which time the patient received a course of amiodarone-based anti-arrhythmic therapy.
No disadvantages seen with dual energy
The greater efficacy of a first shock with dual DCCV was achieved with no apparent disadvantages. There were no differences in post-procedure chest discomfort and no procedure-related adverse events in either arm, Dr. Aymond said.
The rising prevalence of obesity in the United States has created the need for a more effective first-line strategy for AF, noted Dr. Aymond, who presented the results of this study at the annual scientific sessions of the American Heart Association.
Cardioversion, which he characterized as the treatment of choice for AF, “fails to restore sinus rhythm in 20% to 35% of obese patients versus less than 10% of non-obese patients,” he said. The higher failure rate in patients with obesity is becoming a more common clinical issue not only due to the rising rates of obesity but a corresponding rise in AF, which is a related phenomenon.
“The risk of atrial fibrillation is increased by 50% relative to those who are not obese,” Dr. Aymond explained.
In this study, 200 patients at three participating centers were randomized to single DCCV or double DCCV after exclusions that included ventricular tachycardia and respiratory instability. The baseline characteristics were comparable. All 101 patients in the single DCCV group and 99 patients in the dual DCCV group were available for the intention-to-treat analysis.
200 vs. 400 joules delivered across the heart
In the study protocol, patients were fitted with four chest pads, two located adjacent but above the heart and two adjacent but below the heart. For single DCCV, 200 joules of energy were delivered from the upper right pad to the lower left pad across the heart. For dual DCCV, another 200 joules were delivered simultaneously from the upper left to the lower right across the heart. The total dose in the dual DCCV group was 400 joules.
The primary outcome was restoration of sinus rhythm of any duration immediately after DCCV. Safety, including clinical events, was a secondary outcome. Only the patients were blinded to the energy they received.
On univariate analysis, the odds ratio for successful cardioversion with dual DCCV was nearly eightfold higher (OR 7.8; P = .008) than single DCCV. On a simple multivariable analysis, when the researchers controlled for just age, sex, and body mass index, the odds ratio rose (OR 8.5; P = .007).
On a comprehensive multivariable analysis adding control for such characteristics as left ventricular ejection fraction (LVEF), obstructive sleep apnea, and antiarrhythmic drugs, the advantage of dual DCCV climbed above 12-fold (OR 12.6; P = .03).
The study is addressing a relevant and persistent question, said the AHA-invited discussant Jose A. Joglar, MD, program director, Clinical Cardiac Electrophysiology Fellowship, University of Texas Southwestern Medical Center, Dallas.
Dr. Joglar pointed out that alternatives to single DCCV for patients more difficult to cardiovert have been “sought for decades.” He noted that a variety of techniques, including dual DCCV, have been evaluated in small studies and case reports.
Alternatives for obese outlined
Several have shown promise, Dr. Joglar said. As one of several examples, he cited a 20-patient study that randomized patients to adhesive patches, like those employed in the Aymond trial, or handheld paddles. Both patches and paddles were applied with manual pressure while a 200-joule shock was delivered. The proportion of patients who cardioverted on the first shock was almost two times higher in the group after the first shock with the paddles (50% vs. 27%; P = .01). Dr. Joglar said the study supports the principle that 200 joules delivered by adhesive patches is inadequate for treatment of AF in many patients with obesity.
Dr. Joglar also cited studies suggesting that single DCCV delivered with higher energy than 200 joules appears to improve cardioversion success rates, but he indicated that this study with dual DCCV in the front-line setting provides evidence for another alternative.
“This is the first such trial with dual defibrillators as an initial strategy,” he said, calling the groups well matched and the superiority of dual DCCV “impressive.” He cautioned that the study size was well powered for the endpoint but perhaps small for evaluating relative safety.
Yet, “the study adds credibility and confidence for the use of dual DCCV, especially in difficult or refractory patients,” he said. He is less certain that it establishes dual DCCV as a standard first-line therapy in all patients with obesity. This would require additional studies to compare it to other types of strategies such as those he mentioned.
As an option for improving cardioversion in first-line treatment, dual DCCV “can be added to a list of other techniques, such as manual pressure or a higher initial dose with single DCCV,” he said.
Dr. Aymond and Dr. Joglar report no potential conflicts of interest.
AT AHA 2023
Sustained reductions in Lp(a) achieved with novel siRNA drug
In an early phase multicenter clinical study,
The reductions in serum Lp(a) in patients receiving lepodisiran were dose dependent but adverse events were not, said Steven E. Nissen, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine.
Rather, drug-related adverse events “were uncommon and generally similar across all lepodisiran doses and the placebo group,” reported Dr. Nissen, who pointed out that safety and tolerability were the primary endpoints and purpose of this phase 1 study.
Lp(a) strongly associated with CV risk
Similar to LDL cholesterol (LDL-C), elevated levels of serum Lp(a) have been associated with major adverse cardiac events (MACE). In a 2022 review article that summarized pathophysiological, observational, and genetic studies, Lp(a) was found to be implicated in vascular inflammation, atherogenesis, calcification, and thrombosis.
Furthermore, Lp(a) has been associated with residual risk of cardiovascular (CV) events even after tight control of other risk factors, including elevated LDL-C, Dr. Nissen said.
So far, no well-tolerated therapy has been found to be effective for reducing Lp(a), but siRNA is a novel and attractive approach, according to Dr. Nissen, who presented these results at the annual scientific sessions of the American Heart Association. They were also published online in JAMA.
By silencing target genes, siRNA therapies can inhibit a basic step in a given pathological process. In this case, lepodisiran silences the LPA gene to halt encoding of apolipoprotein(a), which plays a key role in Lp(a) production.
Lepodisiran is not the only treatment in development for Lp(a), noted the AHA-invited discussant Michelle L. O’Donoghue, MD, chair in cardiology, Brigham and Women’s Hospital, Boston. She mentioned several other siRNA therapies, including olpasiran that was effective in a phase 2 trial she led and published in the New England Journal of Medicine.
Drugs with different mechanisms, such as the antisense oligonucleotide pelacarsen, showed activity when tested earlier this year in a phase 1 study. No study has yet been conducted to link reductions in Lp(a) with CV event risk reduction.
The current study with lepodisiran was conducted with the participation of five clinical research sites in the United States and Singapore. Participants between the ages of 18 and 65 years were enrolled if they had a serum Lp(a) of at least 75 nmol/L (30 mg/dL), which is considered moderately elevated.
They were excluded if they had CV disease or significant risk factors, including a blood pressure greater than 160/40 mm Hg, impaired renal function (eGFR < 60 mL/min per 1.73 m2), or tobacco use (> 10 cigarettes/day).
Of 340 candidates screened, 48 were randomly assigned to one placebo or six lepodisiran groups. There were 12 participants in the placebo group and 6 in each of the lepodisiran dosing groups (4 mg, 12 mg, 32 mg, 96 mg, 304 mg, and 608 mg). All doses and placebo were administered subcutaneously one time with a planned follow-up of up to 48 weeks.
Safety profile is placebo-like
The single most common adverse event, shared by those randomly assigned to placebo, was injection-site reaction. There were no adverse events, including laboratory abnormalities, that were persistent and clearly different for those assigned to any dose of lepodisiran relative to placebo.
The maximum median percentage change in serum Lp(a) out to day 337 of follow-up was 5% reduction in the placebo group. In the active treatment groups, the reductions were 41% on 4 mg, 59% on 12 mg, 76% on 32 mg, 96% on 304 mg, and 97% on 608 mg.
These reductions were generally sustained for as long as therapy was maintained. Maximal reductions were reached at day 85 in the 4-mg group but were achieved by day 29 in the 605-mg group, Dr. Nissen reported. In fact, serum Lp(a) was undetectable in the 605-mg group at day 29 and remained so until day 281.
Currently, there is no practical treatment for Lp(a). The only potential exception, apheresis, is “cumbersome” to perform and must be repeated for sustained reductions. Niacin and PCSK9 inhibitors are known to provide modest reductions in Lp(a), but Dr. Nissen said they are too modest to expect a meaningful clinical benefit.
Lp(a) not responsive to lifestyle changes
Statins as well as all lifestyle modifications, including diet, have been shown to have “little or no effect,” Dr. Nissen said.
The safety and the evidence so far of sustained Lp(a) lowering has already led to a phase 2 trial, according to Dr. Nissen, but the more important test for the future of lepodisiran will be studies powered to confirm reductions in MACE. Lepodisiran may finally allow that hypothesis to be tested.
“I think a lot of us have been waiting a long time for evidence that we can reliably reduce Lp(a),” said Karol Watson, MD, PhD, who has a research interest in lipids and is a professor of medicine at the University of California, Los Angeles.
Although she conceded that the overwhelming evidence that Lp(a) is a risk factor does not ensure that any specific Lp(a)-lowering therapy will be clinically viable, she suggested this drug is a promising candidate to move this field forward.
“At the highest doses, lepodisiran is not just lowering Lp(a), it appears to be getting rid of it,” she said.
Dr. O’Donoghue said that the phase 1 results suggest lepodisiran might have a somewhat longer duration of action than other siRNA therapies studied for Lp(a) so far, but said larger trials are needed to determine whether the growing number of drugs in this class differ in ways that are clinically meaningful.
Overall, the excitement in this field is probably mostly driven by the fact that there are so many promising therapies for Lp(a) that address the target in so many unique ways. Dr. O’Donoghue cited, as an example, a gene-editing therapy called CTX320 that showed impressive effects in an animal study presented at the AHA meeting as a poster. She called the pipeline for treating Lp(a) “rich.”
Elevated Lp(a) is genetically determined, so levels do not generally change over time, said Donald Lloyd-Jones, MD, chair of the department of preventive medicine, Northwestern Medicine, Chicago.
“It is not affected by your diet. It is not affected by your exercise. What your level is will be the level you will have for the rest of your life,” he said. Generally, it is recommended to have Lp(a) measured just once to more accurately calculate cardiovascular risk, but Dr. Lloyd-Jones predicted that this lipid subfraction might be measured more frequently to verify control if a therapeutic becomes available.
Dr. Nissen agreed. Estimating that 64 million people in the United States have significantly elevated Lp(a), he expects this risk to be addressed as a specific and independent target in CV risk management when and if it becomes treatable.
Dr. Nissen reported financial relationships with Novartis, Silence Therapeutics, and Eli Lilly, which provided funding for this trial. Dr. Watson reported financial relationships with Amgen, Boehringer Ingelheim, Lilly, and Novartis. Dr. Lloyd-Jones disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an early phase multicenter clinical study,
The reductions in serum Lp(a) in patients receiving lepodisiran were dose dependent but adverse events were not, said Steven E. Nissen, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine.
Rather, drug-related adverse events “were uncommon and generally similar across all lepodisiran doses and the placebo group,” reported Dr. Nissen, who pointed out that safety and tolerability were the primary endpoints and purpose of this phase 1 study.
Lp(a) strongly associated with CV risk
Similar to LDL cholesterol (LDL-C), elevated levels of serum Lp(a) have been associated with major adverse cardiac events (MACE). In a 2022 review article that summarized pathophysiological, observational, and genetic studies, Lp(a) was found to be implicated in vascular inflammation, atherogenesis, calcification, and thrombosis.
Furthermore, Lp(a) has been associated with residual risk of cardiovascular (CV) events even after tight control of other risk factors, including elevated LDL-C, Dr. Nissen said.
So far, no well-tolerated therapy has been found to be effective for reducing Lp(a), but siRNA is a novel and attractive approach, according to Dr. Nissen, who presented these results at the annual scientific sessions of the American Heart Association. They were also published online in JAMA.
By silencing target genes, siRNA therapies can inhibit a basic step in a given pathological process. In this case, lepodisiran silences the LPA gene to halt encoding of apolipoprotein(a), which plays a key role in Lp(a) production.
Lepodisiran is not the only treatment in development for Lp(a), noted the AHA-invited discussant Michelle L. O’Donoghue, MD, chair in cardiology, Brigham and Women’s Hospital, Boston. She mentioned several other siRNA therapies, including olpasiran that was effective in a phase 2 trial she led and published in the New England Journal of Medicine.
Drugs with different mechanisms, such as the antisense oligonucleotide pelacarsen, showed activity when tested earlier this year in a phase 1 study. No study has yet been conducted to link reductions in Lp(a) with CV event risk reduction.
The current study with lepodisiran was conducted with the participation of five clinical research sites in the United States and Singapore. Participants between the ages of 18 and 65 years were enrolled if they had a serum Lp(a) of at least 75 nmol/L (30 mg/dL), which is considered moderately elevated.
They were excluded if they had CV disease or significant risk factors, including a blood pressure greater than 160/40 mm Hg, impaired renal function (eGFR < 60 mL/min per 1.73 m2), or tobacco use (> 10 cigarettes/day).
Of 340 candidates screened, 48 were randomly assigned to one placebo or six lepodisiran groups. There were 12 participants in the placebo group and 6 in each of the lepodisiran dosing groups (4 mg, 12 mg, 32 mg, 96 mg, 304 mg, and 608 mg). All doses and placebo were administered subcutaneously one time with a planned follow-up of up to 48 weeks.
Safety profile is placebo-like
The single most common adverse event, shared by those randomly assigned to placebo, was injection-site reaction. There were no adverse events, including laboratory abnormalities, that were persistent and clearly different for those assigned to any dose of lepodisiran relative to placebo.
The maximum median percentage change in serum Lp(a) out to day 337 of follow-up was 5% reduction in the placebo group. In the active treatment groups, the reductions were 41% on 4 mg, 59% on 12 mg, 76% on 32 mg, 96% on 304 mg, and 97% on 608 mg.
These reductions were generally sustained for as long as therapy was maintained. Maximal reductions were reached at day 85 in the 4-mg group but were achieved by day 29 in the 605-mg group, Dr. Nissen reported. In fact, serum Lp(a) was undetectable in the 605-mg group at day 29 and remained so until day 281.
Currently, there is no practical treatment for Lp(a). The only potential exception, apheresis, is “cumbersome” to perform and must be repeated for sustained reductions. Niacin and PCSK9 inhibitors are known to provide modest reductions in Lp(a), but Dr. Nissen said they are too modest to expect a meaningful clinical benefit.
Lp(a) not responsive to lifestyle changes
Statins as well as all lifestyle modifications, including diet, have been shown to have “little or no effect,” Dr. Nissen said.
The safety and the evidence so far of sustained Lp(a) lowering has already led to a phase 2 trial, according to Dr. Nissen, but the more important test for the future of lepodisiran will be studies powered to confirm reductions in MACE. Lepodisiran may finally allow that hypothesis to be tested.
“I think a lot of us have been waiting a long time for evidence that we can reliably reduce Lp(a),” said Karol Watson, MD, PhD, who has a research interest in lipids and is a professor of medicine at the University of California, Los Angeles.
Although she conceded that the overwhelming evidence that Lp(a) is a risk factor does not ensure that any specific Lp(a)-lowering therapy will be clinically viable, she suggested this drug is a promising candidate to move this field forward.
“At the highest doses, lepodisiran is not just lowering Lp(a), it appears to be getting rid of it,” she said.
Dr. O’Donoghue said that the phase 1 results suggest lepodisiran might have a somewhat longer duration of action than other siRNA therapies studied for Lp(a) so far, but said larger trials are needed to determine whether the growing number of drugs in this class differ in ways that are clinically meaningful.
Overall, the excitement in this field is probably mostly driven by the fact that there are so many promising therapies for Lp(a) that address the target in so many unique ways. Dr. O’Donoghue cited, as an example, a gene-editing therapy called CTX320 that showed impressive effects in an animal study presented at the AHA meeting as a poster. She called the pipeline for treating Lp(a) “rich.”
Elevated Lp(a) is genetically determined, so levels do not generally change over time, said Donald Lloyd-Jones, MD, chair of the department of preventive medicine, Northwestern Medicine, Chicago.
“It is not affected by your diet. It is not affected by your exercise. What your level is will be the level you will have for the rest of your life,” he said. Generally, it is recommended to have Lp(a) measured just once to more accurately calculate cardiovascular risk, but Dr. Lloyd-Jones predicted that this lipid subfraction might be measured more frequently to verify control if a therapeutic becomes available.
Dr. Nissen agreed. Estimating that 64 million people in the United States have significantly elevated Lp(a), he expects this risk to be addressed as a specific and independent target in CV risk management when and if it becomes treatable.
Dr. Nissen reported financial relationships with Novartis, Silence Therapeutics, and Eli Lilly, which provided funding for this trial. Dr. Watson reported financial relationships with Amgen, Boehringer Ingelheim, Lilly, and Novartis. Dr. Lloyd-Jones disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an early phase multicenter clinical study,
The reductions in serum Lp(a) in patients receiving lepodisiran were dose dependent but adverse events were not, said Steven E. Nissen, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine.
Rather, drug-related adverse events “were uncommon and generally similar across all lepodisiran doses and the placebo group,” reported Dr. Nissen, who pointed out that safety and tolerability were the primary endpoints and purpose of this phase 1 study.
Lp(a) strongly associated with CV risk
Similar to LDL cholesterol (LDL-C), elevated levels of serum Lp(a) have been associated with major adverse cardiac events (MACE). In a 2022 review article that summarized pathophysiological, observational, and genetic studies, Lp(a) was found to be implicated in vascular inflammation, atherogenesis, calcification, and thrombosis.
Furthermore, Lp(a) has been associated with residual risk of cardiovascular (CV) events even after tight control of other risk factors, including elevated LDL-C, Dr. Nissen said.
So far, no well-tolerated therapy has been found to be effective for reducing Lp(a), but siRNA is a novel and attractive approach, according to Dr. Nissen, who presented these results at the annual scientific sessions of the American Heart Association. They were also published online in JAMA.
By silencing target genes, siRNA therapies can inhibit a basic step in a given pathological process. In this case, lepodisiran silences the LPA gene to halt encoding of apolipoprotein(a), which plays a key role in Lp(a) production.
Lepodisiran is not the only treatment in development for Lp(a), noted the AHA-invited discussant Michelle L. O’Donoghue, MD, chair in cardiology, Brigham and Women’s Hospital, Boston. She mentioned several other siRNA therapies, including olpasiran that was effective in a phase 2 trial she led and published in the New England Journal of Medicine.
Drugs with different mechanisms, such as the antisense oligonucleotide pelacarsen, showed activity when tested earlier this year in a phase 1 study. No study has yet been conducted to link reductions in Lp(a) with CV event risk reduction.
The current study with lepodisiran was conducted with the participation of five clinical research sites in the United States and Singapore. Participants between the ages of 18 and 65 years were enrolled if they had a serum Lp(a) of at least 75 nmol/L (30 mg/dL), which is considered moderately elevated.
They were excluded if they had CV disease or significant risk factors, including a blood pressure greater than 160/40 mm Hg, impaired renal function (eGFR < 60 mL/min per 1.73 m2), or tobacco use (> 10 cigarettes/day).
Of 340 candidates screened, 48 were randomly assigned to one placebo or six lepodisiran groups. There were 12 participants in the placebo group and 6 in each of the lepodisiran dosing groups (4 mg, 12 mg, 32 mg, 96 mg, 304 mg, and 608 mg). All doses and placebo were administered subcutaneously one time with a planned follow-up of up to 48 weeks.
Safety profile is placebo-like
The single most common adverse event, shared by those randomly assigned to placebo, was injection-site reaction. There were no adverse events, including laboratory abnormalities, that were persistent and clearly different for those assigned to any dose of lepodisiran relative to placebo.
The maximum median percentage change in serum Lp(a) out to day 337 of follow-up was 5% reduction in the placebo group. In the active treatment groups, the reductions were 41% on 4 mg, 59% on 12 mg, 76% on 32 mg, 96% on 304 mg, and 97% on 608 mg.
These reductions were generally sustained for as long as therapy was maintained. Maximal reductions were reached at day 85 in the 4-mg group but were achieved by day 29 in the 605-mg group, Dr. Nissen reported. In fact, serum Lp(a) was undetectable in the 605-mg group at day 29 and remained so until day 281.
Currently, there is no practical treatment for Lp(a). The only potential exception, apheresis, is “cumbersome” to perform and must be repeated for sustained reductions. Niacin and PCSK9 inhibitors are known to provide modest reductions in Lp(a), but Dr. Nissen said they are too modest to expect a meaningful clinical benefit.
Lp(a) not responsive to lifestyle changes
Statins as well as all lifestyle modifications, including diet, have been shown to have “little or no effect,” Dr. Nissen said.
The safety and the evidence so far of sustained Lp(a) lowering has already led to a phase 2 trial, according to Dr. Nissen, but the more important test for the future of lepodisiran will be studies powered to confirm reductions in MACE. Lepodisiran may finally allow that hypothesis to be tested.
“I think a lot of us have been waiting a long time for evidence that we can reliably reduce Lp(a),” said Karol Watson, MD, PhD, who has a research interest in lipids and is a professor of medicine at the University of California, Los Angeles.
Although she conceded that the overwhelming evidence that Lp(a) is a risk factor does not ensure that any specific Lp(a)-lowering therapy will be clinically viable, she suggested this drug is a promising candidate to move this field forward.
“At the highest doses, lepodisiran is not just lowering Lp(a), it appears to be getting rid of it,” she said.
Dr. O’Donoghue said that the phase 1 results suggest lepodisiran might have a somewhat longer duration of action than other siRNA therapies studied for Lp(a) so far, but said larger trials are needed to determine whether the growing number of drugs in this class differ in ways that are clinically meaningful.
Overall, the excitement in this field is probably mostly driven by the fact that there are so many promising therapies for Lp(a) that address the target in so many unique ways. Dr. O’Donoghue cited, as an example, a gene-editing therapy called CTX320 that showed impressive effects in an animal study presented at the AHA meeting as a poster. She called the pipeline for treating Lp(a) “rich.”
Elevated Lp(a) is genetically determined, so levels do not generally change over time, said Donald Lloyd-Jones, MD, chair of the department of preventive medicine, Northwestern Medicine, Chicago.
“It is not affected by your diet. It is not affected by your exercise. What your level is will be the level you will have for the rest of your life,” he said. Generally, it is recommended to have Lp(a) measured just once to more accurately calculate cardiovascular risk, but Dr. Lloyd-Jones predicted that this lipid subfraction might be measured more frequently to verify control if a therapeutic becomes available.
Dr. Nissen agreed. Estimating that 64 million people in the United States have significantly elevated Lp(a), he expects this risk to be addressed as a specific and independent target in CV risk management when and if it becomes treatable.
Dr. Nissen reported financial relationships with Novartis, Silence Therapeutics, and Eli Lilly, which provided funding for this trial. Dr. Watson reported financial relationships with Amgen, Boehringer Ingelheim, Lilly, and Novartis. Dr. Lloyd-Jones disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AHA 2023
Angioplasty finally proven beneficial in stable angina: ORBITA-2
PHILADELPHIA – Percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) reduces angina frequency, increases exercise capacity, and improves quality of life, results of a placebo-controlled, randomized trial show, confirming advantages that have never before been proven.
reported Christopher A. Rajkumar, MBBS, an interventional cardiology registrar at the Imperial College Healthcare Trust, London.
Results of the trial, ORBITA-2, were presented at the annual scientific sessions of the American Heart Association and simultaneously published online in the New England Journal of Medicine.
Symptom relief has long been a justification for PCI in patients with stable CAD, but the evidence has been derived from uncontrolled studies, Dr. Rajkumar said. However, the first ORBITA trial, which was also placebo controlled and randomized, failed to show benefit.
Dr. Rajkumar acknowledged that the benefit of PCI in ORBITA-2 was lower than previously reported in nonrandomized trials. He also noted that 59% of patients still had at least some angina symptoms following PCI.
Even though ORBITA-2 proves that PCI is better than no PCI, he agreed that well-informed patients, such as those who wish to avoid an invasive procedure, might still reasonably select antianginal medication over PCI. Current guidelines recommend PCI for patients with refractory angina despite medical therapy.
While Dr. Rajkumar was unwilling to speculate on how these data might change guidelines, he did say that patients with stable CAD and angina “now have a choice of two first-line evidence-based pathways.”
‘Remarkable’ trial
“ORBITA 2 is a rather remarkable trial because my surgical colleagues have been asking me for many decades whether PCI actually works,” said Martin B. Leon, MD, professor of medicine, Columbia University Irving Medical Center, New York. “Now I can say with confidence on the basis of a placebo-controlled trial that PCI certainly does have a favorable impact in patients with documented angina, severe coronary stenosis, and demonstrated ischemia.”
The key enrollment criteria for ORBITA-2 were angina, severe coronary stenosis in at least one vessel, and ischemia on stress imaging or invasive physiology. Unlike the previous ORBITA trial, which was limited to single-vessel disease and did not require objective evidence of ischemia, ORBITA 2 employed change in angina, rather than improved exercise capacity, as its primary endpoint.
Relative to sham PCI, patients randomly assigned to an interventional procedure had a more than twofold increase in the odds ratio of improved angina control (OR, 2.2; P < .001) based on a patient scoring system that captured angina symptoms as well as angina medication use on a smartphone application.
The advantage of PCI over sham PCI was also significant for all secondary outcomes. These included a nearly fourfold greater (OR, 3.76; P < .001) likelihood of improvement in the Canadian Cardiovascular Society angina grade and a 1-minute increase (from 10 min. 40 seconds to 11 min. 40 seconds) in treadmill exercise time (P = .008).
On quality of life measured with the self-assessment questionnaire and the EQ-5D-5L, almost all endpoints were highly statistically significant in favor of PCI (typically on the level of P < .001).
The study had a bold design: At enrollment patients stopped all antianginal medications to undergo dobutamine echocardiography and other baseline tests. They were stopped again 2 weeks later, when patients were randomized.
With a study protocol that enrolled patients off medication, “we intentionally diverged from the clinical guidelines,” Dr. Rajkumar said.
Of the 439 patients enrolled, 301 were randomly assigned at the end of the 2-week period, when patients were already sedated. Control patients remained sedated for at least 15 minutes. All 151 of those randomized to PCI and the 150 control patients were available for the intent-to-treat analysis at the end of 12 weeks.
The novel angina symptom burden score was created from daily angina episodes and units of daily antianginal medication captured on the smartphone app. On an ordinal scale, a score of 0 on any given day represented no anginal symptoms and no antianginal medication.
As angina severity or medication use increased, it raised the daily scores. If there was unacceptable angina (requiring the patient to be removed from the blind), acute coronary syndrome, or death, it produced the highest scores, which reached a maximum of 79.
The favorable OR for a lower symptom burden in the PCI group reflected a relative reduction in angina observed the first day after the procedure. Over the entire follow-up, more patients in the PCI group had an angina score of 0 and more of those who had angina did not take antianginal medications.
This objective evidence that PCI reduces symptoms and improves quality of life in patients with angina and stable CAD was met at the AHA late-breaking session with a sustained ovation.
ORBITA-2 addresses ORBITA criticisms
Connie N. Hess, MD, the AHA-invited discussant and an interventional cardiologist at the University of Colorado Medicine, Aurora, provided perspective on the differences between ORBITA 2 and ORBITA, which she said “addressed a fundamentally different hypothesis” by focusing on angina rather than exercise capacity.
Of the criticisms of the original ORBITA, which Dr. Hess noted was the first sham-controlled PCI trial ever conducted in stable CAD, one is that patients with multivessel disease were excluded, another was that objectively proven ischemia was not required, and a third was that the study of 6 weeks had a short duration.
“ORBITA 2 addressed many of these concerns,” Dr. Hess said, but, when noting that 80% of patients in the newer trial still had single vessel disease, she questioned whether the true effect of PCI for improving symptoms might still be underestimated.
ORBITA-2 was supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre, the Medical Research Council, NIHR, the British Heart Foundation, Philips, and St. Mary’s Coronary Flow Trust. Dr. Rajkumar reported relevant financial relationships. Dr. Leon reported financial relationships with Abbott Vascular, Anteris, Boston Scientific, Edwards Lifesciences, Foldax, and Medtronic. Dr. Hess has financial relationships with more than 20 pharmaceutical companies, but none related specifically to this presentation.
PHILADELPHIA – Percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) reduces angina frequency, increases exercise capacity, and improves quality of life, results of a placebo-controlled, randomized trial show, confirming advantages that have never before been proven.
reported Christopher A. Rajkumar, MBBS, an interventional cardiology registrar at the Imperial College Healthcare Trust, London.
Results of the trial, ORBITA-2, were presented at the annual scientific sessions of the American Heart Association and simultaneously published online in the New England Journal of Medicine.
Symptom relief has long been a justification for PCI in patients with stable CAD, but the evidence has been derived from uncontrolled studies, Dr. Rajkumar said. However, the first ORBITA trial, which was also placebo controlled and randomized, failed to show benefit.
Dr. Rajkumar acknowledged that the benefit of PCI in ORBITA-2 was lower than previously reported in nonrandomized trials. He also noted that 59% of patients still had at least some angina symptoms following PCI.
Even though ORBITA-2 proves that PCI is better than no PCI, he agreed that well-informed patients, such as those who wish to avoid an invasive procedure, might still reasonably select antianginal medication over PCI. Current guidelines recommend PCI for patients with refractory angina despite medical therapy.
While Dr. Rajkumar was unwilling to speculate on how these data might change guidelines, he did say that patients with stable CAD and angina “now have a choice of two first-line evidence-based pathways.”
‘Remarkable’ trial
“ORBITA 2 is a rather remarkable trial because my surgical colleagues have been asking me for many decades whether PCI actually works,” said Martin B. Leon, MD, professor of medicine, Columbia University Irving Medical Center, New York. “Now I can say with confidence on the basis of a placebo-controlled trial that PCI certainly does have a favorable impact in patients with documented angina, severe coronary stenosis, and demonstrated ischemia.”
The key enrollment criteria for ORBITA-2 were angina, severe coronary stenosis in at least one vessel, and ischemia on stress imaging or invasive physiology. Unlike the previous ORBITA trial, which was limited to single-vessel disease and did not require objective evidence of ischemia, ORBITA 2 employed change in angina, rather than improved exercise capacity, as its primary endpoint.
Relative to sham PCI, patients randomly assigned to an interventional procedure had a more than twofold increase in the odds ratio of improved angina control (OR, 2.2; P < .001) based on a patient scoring system that captured angina symptoms as well as angina medication use on a smartphone application.
The advantage of PCI over sham PCI was also significant for all secondary outcomes. These included a nearly fourfold greater (OR, 3.76; P < .001) likelihood of improvement in the Canadian Cardiovascular Society angina grade and a 1-minute increase (from 10 min. 40 seconds to 11 min. 40 seconds) in treadmill exercise time (P = .008).
On quality of life measured with the self-assessment questionnaire and the EQ-5D-5L, almost all endpoints were highly statistically significant in favor of PCI (typically on the level of P < .001).
The study had a bold design: At enrollment patients stopped all antianginal medications to undergo dobutamine echocardiography and other baseline tests. They were stopped again 2 weeks later, when patients were randomized.
With a study protocol that enrolled patients off medication, “we intentionally diverged from the clinical guidelines,” Dr. Rajkumar said.
Of the 439 patients enrolled, 301 were randomly assigned at the end of the 2-week period, when patients were already sedated. Control patients remained sedated for at least 15 minutes. All 151 of those randomized to PCI and the 150 control patients were available for the intent-to-treat analysis at the end of 12 weeks.
The novel angina symptom burden score was created from daily angina episodes and units of daily antianginal medication captured on the smartphone app. On an ordinal scale, a score of 0 on any given day represented no anginal symptoms and no antianginal medication.
As angina severity or medication use increased, it raised the daily scores. If there was unacceptable angina (requiring the patient to be removed from the blind), acute coronary syndrome, or death, it produced the highest scores, which reached a maximum of 79.
The favorable OR for a lower symptom burden in the PCI group reflected a relative reduction in angina observed the first day after the procedure. Over the entire follow-up, more patients in the PCI group had an angina score of 0 and more of those who had angina did not take antianginal medications.
This objective evidence that PCI reduces symptoms and improves quality of life in patients with angina and stable CAD was met at the AHA late-breaking session with a sustained ovation.
ORBITA-2 addresses ORBITA criticisms
Connie N. Hess, MD, the AHA-invited discussant and an interventional cardiologist at the University of Colorado Medicine, Aurora, provided perspective on the differences between ORBITA 2 and ORBITA, which she said “addressed a fundamentally different hypothesis” by focusing on angina rather than exercise capacity.
Of the criticisms of the original ORBITA, which Dr. Hess noted was the first sham-controlled PCI trial ever conducted in stable CAD, one is that patients with multivessel disease were excluded, another was that objectively proven ischemia was not required, and a third was that the study of 6 weeks had a short duration.
“ORBITA 2 addressed many of these concerns,” Dr. Hess said, but, when noting that 80% of patients in the newer trial still had single vessel disease, she questioned whether the true effect of PCI for improving symptoms might still be underestimated.
ORBITA-2 was supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre, the Medical Research Council, NIHR, the British Heart Foundation, Philips, and St. Mary’s Coronary Flow Trust. Dr. Rajkumar reported relevant financial relationships. Dr. Leon reported financial relationships with Abbott Vascular, Anteris, Boston Scientific, Edwards Lifesciences, Foldax, and Medtronic. Dr. Hess has financial relationships with more than 20 pharmaceutical companies, but none related specifically to this presentation.
PHILADELPHIA – Percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) reduces angina frequency, increases exercise capacity, and improves quality of life, results of a placebo-controlled, randomized trial show, confirming advantages that have never before been proven.
reported Christopher A. Rajkumar, MBBS, an interventional cardiology registrar at the Imperial College Healthcare Trust, London.
Results of the trial, ORBITA-2, were presented at the annual scientific sessions of the American Heart Association and simultaneously published online in the New England Journal of Medicine.
Symptom relief has long been a justification for PCI in patients with stable CAD, but the evidence has been derived from uncontrolled studies, Dr. Rajkumar said. However, the first ORBITA trial, which was also placebo controlled and randomized, failed to show benefit.
Dr. Rajkumar acknowledged that the benefit of PCI in ORBITA-2 was lower than previously reported in nonrandomized trials. He also noted that 59% of patients still had at least some angina symptoms following PCI.
Even though ORBITA-2 proves that PCI is better than no PCI, he agreed that well-informed patients, such as those who wish to avoid an invasive procedure, might still reasonably select antianginal medication over PCI. Current guidelines recommend PCI for patients with refractory angina despite medical therapy.
While Dr. Rajkumar was unwilling to speculate on how these data might change guidelines, he did say that patients with stable CAD and angina “now have a choice of two first-line evidence-based pathways.”
‘Remarkable’ trial
“ORBITA 2 is a rather remarkable trial because my surgical colleagues have been asking me for many decades whether PCI actually works,” said Martin B. Leon, MD, professor of medicine, Columbia University Irving Medical Center, New York. “Now I can say with confidence on the basis of a placebo-controlled trial that PCI certainly does have a favorable impact in patients with documented angina, severe coronary stenosis, and demonstrated ischemia.”
The key enrollment criteria for ORBITA-2 were angina, severe coronary stenosis in at least one vessel, and ischemia on stress imaging or invasive physiology. Unlike the previous ORBITA trial, which was limited to single-vessel disease and did not require objective evidence of ischemia, ORBITA 2 employed change in angina, rather than improved exercise capacity, as its primary endpoint.
Relative to sham PCI, patients randomly assigned to an interventional procedure had a more than twofold increase in the odds ratio of improved angina control (OR, 2.2; P < .001) based on a patient scoring system that captured angina symptoms as well as angina medication use on a smartphone application.
The advantage of PCI over sham PCI was also significant for all secondary outcomes. These included a nearly fourfold greater (OR, 3.76; P < .001) likelihood of improvement in the Canadian Cardiovascular Society angina grade and a 1-minute increase (from 10 min. 40 seconds to 11 min. 40 seconds) in treadmill exercise time (P = .008).
On quality of life measured with the self-assessment questionnaire and the EQ-5D-5L, almost all endpoints were highly statistically significant in favor of PCI (typically on the level of P < .001).
The study had a bold design: At enrollment patients stopped all antianginal medications to undergo dobutamine echocardiography and other baseline tests. They were stopped again 2 weeks later, when patients were randomized.
With a study protocol that enrolled patients off medication, “we intentionally diverged from the clinical guidelines,” Dr. Rajkumar said.
Of the 439 patients enrolled, 301 were randomly assigned at the end of the 2-week period, when patients were already sedated. Control patients remained sedated for at least 15 minutes. All 151 of those randomized to PCI and the 150 control patients were available for the intent-to-treat analysis at the end of 12 weeks.
The novel angina symptom burden score was created from daily angina episodes and units of daily antianginal medication captured on the smartphone app. On an ordinal scale, a score of 0 on any given day represented no anginal symptoms and no antianginal medication.
As angina severity or medication use increased, it raised the daily scores. If there was unacceptable angina (requiring the patient to be removed from the blind), acute coronary syndrome, or death, it produced the highest scores, which reached a maximum of 79.
The favorable OR for a lower symptom burden in the PCI group reflected a relative reduction in angina observed the first day after the procedure. Over the entire follow-up, more patients in the PCI group had an angina score of 0 and more of those who had angina did not take antianginal medications.
This objective evidence that PCI reduces symptoms and improves quality of life in patients with angina and stable CAD was met at the AHA late-breaking session with a sustained ovation.
ORBITA-2 addresses ORBITA criticisms
Connie N. Hess, MD, the AHA-invited discussant and an interventional cardiologist at the University of Colorado Medicine, Aurora, provided perspective on the differences between ORBITA 2 and ORBITA, which she said “addressed a fundamentally different hypothesis” by focusing on angina rather than exercise capacity.
Of the criticisms of the original ORBITA, which Dr. Hess noted was the first sham-controlled PCI trial ever conducted in stable CAD, one is that patients with multivessel disease were excluded, another was that objectively proven ischemia was not required, and a third was that the study of 6 weeks had a short duration.
“ORBITA 2 addressed many of these concerns,” Dr. Hess said, but, when noting that 80% of patients in the newer trial still had single vessel disease, she questioned whether the true effect of PCI for improving symptoms might still be underestimated.
ORBITA-2 was supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre, the Medical Research Council, NIHR, the British Heart Foundation, Philips, and St. Mary’s Coronary Flow Trust. Dr. Rajkumar reported relevant financial relationships. Dr. Leon reported financial relationships with Abbott Vascular, Anteris, Boston Scientific, Edwards Lifesciences, Foldax, and Medtronic. Dr. Hess has financial relationships with more than 20 pharmaceutical companies, but none related specifically to this presentation.
AT AHA 2023
Prurigo nodularis diagnosis delay in skin of color gains added significance
NEW YORK – according to an expert evaluating current approaches at the Skin of Color Update 2023.
“As dermatologists, prurigo nodularis is one of the most severe diseases we treat, said Shawn G. Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore. Now with one approved therapy and more coming, “it offers one of the most important opportunities we have to dramatically improve someone’s entire life.”
Prior to the September 2022 approval of dupilumab for the treatment of prurigo nodularis (the first treatment approved for this indication), Dr. Kwatra said that the limited options for control of pruritus made him anxious. Prurigo nodularis is characterized by highly itchy nodules that can produce symptoms patients describe as unbearable.
Itch typically severe
On a scale for which 10 represents the worst itch imaginable, scores of 8 or greater are not unusual, according to Dr. Kwatra. Nodules on the trunk and the extensor surfaces of the arms and legs are characteristic, but the persistent itch is the immediate target of treatment once the diagnosis is made. For that reason, he urged clinicians to be familiar with the presentation in patients with darker skin types to reduce time to treatment.
In addition to the difficulty of seeing the characteristic red that is typical of erythema in lighter skin, patients with darker skin types tend to have larger nodules that might vary in shape relative to lighter skin types, Dr. Kwatra said. Given that the presentation of prurigo nodularis is highly heterogeneous even among the same skin types, the nuances in patients with darker skin can be that much more confusing for those without prior experience.
Among Blacks in particular, the nodules in some cases “can be huge,” he added. “They can almost look like keloids due to their thickened and fibrotic appearance.”
Phenotypes appear to be racially linked
In Black patients, the appearance can vary enough relative to lighter skin individuals, that “there seems to be something a little bit different going on,” he said, and this is, in fact, supported by a cluster analysis of circulating biomarkers reported by Dr. Kwatra and colleagues in 2022, in the Journal of Investigative Dermatology.
In that study, the biomarker profile distinguished two distinct groups. Whites were more common in a cluster with relatively low expression of inflammatory markers (cluster 1), while Blacks were more common in a cluster with an inflammatory plasma profile (cluster 2), with higher relative expression of multiple cytokines, C-reactive protein, eosinophils, and other markers of up-regulated inflammation.
In addition to a lower rate of myelopathy in cluster 2 than cluster 1 (18% vs. 67%; P = .028), patients in cluster 2 had a significantly worse itch than those in cluster 1 on the Numeric Rating Scale for itch and a significantly lower quality of life based on the Dermatology Life Quality Index score.
Other work at Dr. Kwatra’s center that is based on genetic sequencing has provided evidence that Blacks – and Asians to a lesser extent – are predisposed genetically to develop nodules, perhaps explaining why the nodules tend to be larger than those seen in Whites.
The significance of the evidence that prurigo nodularis is associated with a more up-regulated inflammatory profile in Blacks than in Whites is that they might be particularly likely to respond to dupilumab or other targeted immunomodulating therapies that are in development, according to Dr. Kwatra. Although he did not provide data on response by race, he did provide several case examples of complete itch control following dupilumab therapy in Black patients.
In his experience, high levels of blood eosinophils and other inflammatory markers are predictors of response to dupilumab regardless of skin type, but he expressed concern that time to diagnosis is sometimes longer in Black patients if the nuances of disease expression are not appreciated.
For treating prurigo nodularis in Blacks as well as Whites, Dr. Kwatra suggested that clinicians stay current with what he predicted will be a growing array of treatment options. He did not discuss nemolizumab, an interleukin-31 receptor alpha antagonist. Soon after the meeting, results of a phase 3 trial of nemolizumab in patients with moderate to severe prurigo nodularis were published in the New England Journal of Medicine. (Dr. Kwatra is the lead author of the study but did not specifically discuss this treatment at the meeting.)
In the international placebo-controlled trial, called OLYMPIA 2, treatment was associated with a significant reduction in the signs and symptoms of prurigo nodularis, including reductions in itch, at 16 weeks, although only 4% of patients in the study were Black.
Given the expanding array of therapies, the message of considering prurigo nodularis in Black patients in order to accelerate the time to diagnosis is timely, Andrew F. Alexis, MD, MPH, professor of clinical dermatology and vice-chair for diversity and inclusion for the department of dermatology, Weill Cornell Medicine, New York.
“Current studies suggest a higher prevalence and greater severity of prurigo nodularis among Black patients compared to White patients,” said Dr. Alexis, agreeing with Dr. Kwatra. Referring to evidence that Blacks might mount a greater inflammatory response to prurigo nodularis than Whites, Dr. Alexis called for “a better understanding of the pathomechanisms” of this disease in order “to address unmet needs and reduce disparities for our diverse population of patients who suffer from prurigo nodularis.’
Dr. Kwatra reported financial relationships with AbbVie, Amgen, Arcutis, ASLAN, Cara, Castle Biosciences, Celldex, Galderma, Incyte, Johnson & Johnson, LEO pharma, Novartis, Pfizer, Regeneron, and Sanofi.
NEW YORK – according to an expert evaluating current approaches at the Skin of Color Update 2023.
“As dermatologists, prurigo nodularis is one of the most severe diseases we treat, said Shawn G. Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore. Now with one approved therapy and more coming, “it offers one of the most important opportunities we have to dramatically improve someone’s entire life.”
Prior to the September 2022 approval of dupilumab for the treatment of prurigo nodularis (the first treatment approved for this indication), Dr. Kwatra said that the limited options for control of pruritus made him anxious. Prurigo nodularis is characterized by highly itchy nodules that can produce symptoms patients describe as unbearable.
Itch typically severe
On a scale for which 10 represents the worst itch imaginable, scores of 8 or greater are not unusual, according to Dr. Kwatra. Nodules on the trunk and the extensor surfaces of the arms and legs are characteristic, but the persistent itch is the immediate target of treatment once the diagnosis is made. For that reason, he urged clinicians to be familiar with the presentation in patients with darker skin types to reduce time to treatment.
In addition to the difficulty of seeing the characteristic red that is typical of erythema in lighter skin, patients with darker skin types tend to have larger nodules that might vary in shape relative to lighter skin types, Dr. Kwatra said. Given that the presentation of prurigo nodularis is highly heterogeneous even among the same skin types, the nuances in patients with darker skin can be that much more confusing for those without prior experience.
Among Blacks in particular, the nodules in some cases “can be huge,” he added. “They can almost look like keloids due to their thickened and fibrotic appearance.”
Phenotypes appear to be racially linked
In Black patients, the appearance can vary enough relative to lighter skin individuals, that “there seems to be something a little bit different going on,” he said, and this is, in fact, supported by a cluster analysis of circulating biomarkers reported by Dr. Kwatra and colleagues in 2022, in the Journal of Investigative Dermatology.
In that study, the biomarker profile distinguished two distinct groups. Whites were more common in a cluster with relatively low expression of inflammatory markers (cluster 1), while Blacks were more common in a cluster with an inflammatory plasma profile (cluster 2), with higher relative expression of multiple cytokines, C-reactive protein, eosinophils, and other markers of up-regulated inflammation.
In addition to a lower rate of myelopathy in cluster 2 than cluster 1 (18% vs. 67%; P = .028), patients in cluster 2 had a significantly worse itch than those in cluster 1 on the Numeric Rating Scale for itch and a significantly lower quality of life based on the Dermatology Life Quality Index score.
Other work at Dr. Kwatra’s center that is based on genetic sequencing has provided evidence that Blacks – and Asians to a lesser extent – are predisposed genetically to develop nodules, perhaps explaining why the nodules tend to be larger than those seen in Whites.
The significance of the evidence that prurigo nodularis is associated with a more up-regulated inflammatory profile in Blacks than in Whites is that they might be particularly likely to respond to dupilumab or other targeted immunomodulating therapies that are in development, according to Dr. Kwatra. Although he did not provide data on response by race, he did provide several case examples of complete itch control following dupilumab therapy in Black patients.
In his experience, high levels of blood eosinophils and other inflammatory markers are predictors of response to dupilumab regardless of skin type, but he expressed concern that time to diagnosis is sometimes longer in Black patients if the nuances of disease expression are not appreciated.
For treating prurigo nodularis in Blacks as well as Whites, Dr. Kwatra suggested that clinicians stay current with what he predicted will be a growing array of treatment options. He did not discuss nemolizumab, an interleukin-31 receptor alpha antagonist. Soon after the meeting, results of a phase 3 trial of nemolizumab in patients with moderate to severe prurigo nodularis were published in the New England Journal of Medicine. (Dr. Kwatra is the lead author of the study but did not specifically discuss this treatment at the meeting.)
In the international placebo-controlled trial, called OLYMPIA 2, treatment was associated with a significant reduction in the signs and symptoms of prurigo nodularis, including reductions in itch, at 16 weeks, although only 4% of patients in the study were Black.
Given the expanding array of therapies, the message of considering prurigo nodularis in Black patients in order to accelerate the time to diagnosis is timely, Andrew F. Alexis, MD, MPH, professor of clinical dermatology and vice-chair for diversity and inclusion for the department of dermatology, Weill Cornell Medicine, New York.
“Current studies suggest a higher prevalence and greater severity of prurigo nodularis among Black patients compared to White patients,” said Dr. Alexis, agreeing with Dr. Kwatra. Referring to evidence that Blacks might mount a greater inflammatory response to prurigo nodularis than Whites, Dr. Alexis called for “a better understanding of the pathomechanisms” of this disease in order “to address unmet needs and reduce disparities for our diverse population of patients who suffer from prurigo nodularis.’
Dr. Kwatra reported financial relationships with AbbVie, Amgen, Arcutis, ASLAN, Cara, Castle Biosciences, Celldex, Galderma, Incyte, Johnson & Johnson, LEO pharma, Novartis, Pfizer, Regeneron, and Sanofi.
NEW YORK – according to an expert evaluating current approaches at the Skin of Color Update 2023.
“As dermatologists, prurigo nodularis is one of the most severe diseases we treat, said Shawn G. Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore. Now with one approved therapy and more coming, “it offers one of the most important opportunities we have to dramatically improve someone’s entire life.”
Prior to the September 2022 approval of dupilumab for the treatment of prurigo nodularis (the first treatment approved for this indication), Dr. Kwatra said that the limited options for control of pruritus made him anxious. Prurigo nodularis is characterized by highly itchy nodules that can produce symptoms patients describe as unbearable.
Itch typically severe
On a scale for which 10 represents the worst itch imaginable, scores of 8 or greater are not unusual, according to Dr. Kwatra. Nodules on the trunk and the extensor surfaces of the arms and legs are characteristic, but the persistent itch is the immediate target of treatment once the diagnosis is made. For that reason, he urged clinicians to be familiar with the presentation in patients with darker skin types to reduce time to treatment.
In addition to the difficulty of seeing the characteristic red that is typical of erythema in lighter skin, patients with darker skin types tend to have larger nodules that might vary in shape relative to lighter skin types, Dr. Kwatra said. Given that the presentation of prurigo nodularis is highly heterogeneous even among the same skin types, the nuances in patients with darker skin can be that much more confusing for those without prior experience.
Among Blacks in particular, the nodules in some cases “can be huge,” he added. “They can almost look like keloids due to their thickened and fibrotic appearance.”
Phenotypes appear to be racially linked
In Black patients, the appearance can vary enough relative to lighter skin individuals, that “there seems to be something a little bit different going on,” he said, and this is, in fact, supported by a cluster analysis of circulating biomarkers reported by Dr. Kwatra and colleagues in 2022, in the Journal of Investigative Dermatology.
In that study, the biomarker profile distinguished two distinct groups. Whites were more common in a cluster with relatively low expression of inflammatory markers (cluster 1), while Blacks were more common in a cluster with an inflammatory plasma profile (cluster 2), with higher relative expression of multiple cytokines, C-reactive protein, eosinophils, and other markers of up-regulated inflammation.
In addition to a lower rate of myelopathy in cluster 2 than cluster 1 (18% vs. 67%; P = .028), patients in cluster 2 had a significantly worse itch than those in cluster 1 on the Numeric Rating Scale for itch and a significantly lower quality of life based on the Dermatology Life Quality Index score.
Other work at Dr. Kwatra’s center that is based on genetic sequencing has provided evidence that Blacks – and Asians to a lesser extent – are predisposed genetically to develop nodules, perhaps explaining why the nodules tend to be larger than those seen in Whites.
The significance of the evidence that prurigo nodularis is associated with a more up-regulated inflammatory profile in Blacks than in Whites is that they might be particularly likely to respond to dupilumab or other targeted immunomodulating therapies that are in development, according to Dr. Kwatra. Although he did not provide data on response by race, he did provide several case examples of complete itch control following dupilumab therapy in Black patients.
In his experience, high levels of blood eosinophils and other inflammatory markers are predictors of response to dupilumab regardless of skin type, but he expressed concern that time to diagnosis is sometimes longer in Black patients if the nuances of disease expression are not appreciated.
For treating prurigo nodularis in Blacks as well as Whites, Dr. Kwatra suggested that clinicians stay current with what he predicted will be a growing array of treatment options. He did not discuss nemolizumab, an interleukin-31 receptor alpha antagonist. Soon after the meeting, results of a phase 3 trial of nemolizumab in patients with moderate to severe prurigo nodularis were published in the New England Journal of Medicine. (Dr. Kwatra is the lead author of the study but did not specifically discuss this treatment at the meeting.)
In the international placebo-controlled trial, called OLYMPIA 2, treatment was associated with a significant reduction in the signs and symptoms of prurigo nodularis, including reductions in itch, at 16 weeks, although only 4% of patients in the study were Black.
Given the expanding array of therapies, the message of considering prurigo nodularis in Black patients in order to accelerate the time to diagnosis is timely, Andrew F. Alexis, MD, MPH, professor of clinical dermatology and vice-chair for diversity and inclusion for the department of dermatology, Weill Cornell Medicine, New York.
“Current studies suggest a higher prevalence and greater severity of prurigo nodularis among Black patients compared to White patients,” said Dr. Alexis, agreeing with Dr. Kwatra. Referring to evidence that Blacks might mount a greater inflammatory response to prurigo nodularis than Whites, Dr. Alexis called for “a better understanding of the pathomechanisms” of this disease in order “to address unmet needs and reduce disparities for our diverse population of patients who suffer from prurigo nodularis.’
Dr. Kwatra reported financial relationships with AbbVie, Amgen, Arcutis, ASLAN, Cara, Castle Biosciences, Celldex, Galderma, Incyte, Johnson & Johnson, LEO pharma, Novartis, Pfizer, Regeneron, and Sanofi.
AT SOC 2023