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First-in-class TYK inhibitor shows durable effect for psoriasis
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Eurocentric standards of beauty are no longer dominant, experts agree
Addressing current standards of beauty at the Skin of Color Update 2021, dermatologists speaking about attitudes within four ethnic groups recounted a similar story: .
This change is relevant to dermatologists consulting with patients for cosmetic procedures. Four dermatologists who recounted the types of procedures their patients are requesting each reported that more patients are seeking cosmetic enhancements that accentuate rather than modify ethnic features.
Lips in Black, Asian, and Arab ethnic groups are just one example.
“Where several years ago, the conversation was really about lip reductions – how we can deemphasize the lip – I am now seeing lots of women of color coming in to ask about lip augmentation, looking to highlight their lips as a point of beauty,” reported Michelle Henry, MD, a dermatologist who practices in New York City.
She is not alone. Others participating on the same panel spoke of a growing interest among their patients to maintain or even emphasize the same ethnic features – including but not limited to lip shape and size that they were once anxious to modify.
In Asian patients, “the goal is not to Westernize,” agreed Annie Chiu, MD, a dermatologist who practices in North Redondo Beach, Calif. For lips, she spoke of the “50-50 ratio” of upper and lower lip symmetry that is consistent with a traditional Asian characteristic.
Like Dr. Henry, Dr. Chiu said that many requests for cosmetic work now involve accentuating Asian features, such as the oval shape of the face, rather than steps to modify this shape. This is a relatively recent change.
“I am finding that more of my patients want to improve the esthetic balance to optimize the appearance within their own ethnicity,” she said.
In the United Arab Emirates (UAE), Hassan Galadari, MD, an American-trained physician who is assistant professor of dermatology at the UAE University in Dubai, recently conducted a poll of his patients. In order of importance, full lips came after wide eyes, a straight nose, and a sharp jaw line. Full cheeks and a round face completed a list that diverges from the California-blond prototype.
Although Angelina Jolie was selected over several Lebanese actresses as a first choice for an icon of beauty in this same poll, Dr. Galadari pointed out that this actress has many of the features, including wide eyes, a straight nose, and full lips, that are consistent with traditional features of Arab beauty.
Perceptions of beauty are not just changing within ethnic groups but reflected in mass culture. Dr. Henry pointed to a published comparison of the “World’s Most Beautiful” list from People magazine in 2017 relative to 1990. Of the 50 celebrities on the list in 1990, 88% were Fitzpatrick skin types I-III. Only 12% were types IV-VI, which increased to almost 30% of the 135 celebrities on the list in 2017 (P = .01). In 1990, just one celebrity (2%) was of mixed race, which increased to 10.4% in 2017.
Among Hispanic women, the changes in attitude are perhaps best captured among younger relative to older patients requesting cosmetic work, according to Maritza I. Perez, MD, professor of dermatology, University of Connecticut, Farmington. She said that her younger patients are less likely to seek rhinoplasty and blepharoplasty relative to her older patients, a reflection perhaps of comfort with their natural looks.
However, “the celebration of Latinas as beautiful, seductive, and sexual is hardly new,” she said, indicating that younger Hispanic patients are probably not driven to modify their ethnic features because they are already widely admired. “Six of the 10 women crowned Miss Universe in the last decade were from Latin American countries,” she noted.
The general willingness of patients within ethnic groups and society as a whole to see ethnic features as admirable and attractive was generally regarded by all the panelists as a positive development.
Dr. Henry, who said she was “encouraged” by such trends as “the natural hair movement” and diminishing interest among her darker patients in lightening skin pigment, said, “I definitely see a change among my patients in regard to their goals.”
For clinicians offering consults to patients seeking cosmetic work, Dr. Henry recommended being aware and sensitive to this evolution in order to offer appropriate care.
Dr. Chiu, emphasizing the pride that many of her patients take in their Asian features, made the same recommendation. She credited globalization and social media for attitudes that have allowed an embrace of what are now far more inclusive standards of beauty.
Dr. Henry reports financial relationships with Allergan and Merz. Dr. Chiu has financial relationships with AbbVie, Cynosure, Merz, Revance, and Solta. Dr. Galadari reports financial relationships with nine pharmaceutical companies, including Allergan, Merz, Revance, and Fillmed Laboratories. Dr. Perez reports no relevant conflicts of interest.
Addressing current standards of beauty at the Skin of Color Update 2021, dermatologists speaking about attitudes within four ethnic groups recounted a similar story: .
This change is relevant to dermatologists consulting with patients for cosmetic procedures. Four dermatologists who recounted the types of procedures their patients are requesting each reported that more patients are seeking cosmetic enhancements that accentuate rather than modify ethnic features.
Lips in Black, Asian, and Arab ethnic groups are just one example.
“Where several years ago, the conversation was really about lip reductions – how we can deemphasize the lip – I am now seeing lots of women of color coming in to ask about lip augmentation, looking to highlight their lips as a point of beauty,” reported Michelle Henry, MD, a dermatologist who practices in New York City.
She is not alone. Others participating on the same panel spoke of a growing interest among their patients to maintain or even emphasize the same ethnic features – including but not limited to lip shape and size that they were once anxious to modify.
In Asian patients, “the goal is not to Westernize,” agreed Annie Chiu, MD, a dermatologist who practices in North Redondo Beach, Calif. For lips, she spoke of the “50-50 ratio” of upper and lower lip symmetry that is consistent with a traditional Asian characteristic.
Like Dr. Henry, Dr. Chiu said that many requests for cosmetic work now involve accentuating Asian features, such as the oval shape of the face, rather than steps to modify this shape. This is a relatively recent change.
“I am finding that more of my patients want to improve the esthetic balance to optimize the appearance within their own ethnicity,” she said.
In the United Arab Emirates (UAE), Hassan Galadari, MD, an American-trained physician who is assistant professor of dermatology at the UAE University in Dubai, recently conducted a poll of his patients. In order of importance, full lips came after wide eyes, a straight nose, and a sharp jaw line. Full cheeks and a round face completed a list that diverges from the California-blond prototype.
Although Angelina Jolie was selected over several Lebanese actresses as a first choice for an icon of beauty in this same poll, Dr. Galadari pointed out that this actress has many of the features, including wide eyes, a straight nose, and full lips, that are consistent with traditional features of Arab beauty.
Perceptions of beauty are not just changing within ethnic groups but reflected in mass culture. Dr. Henry pointed to a published comparison of the “World’s Most Beautiful” list from People magazine in 2017 relative to 1990. Of the 50 celebrities on the list in 1990, 88% were Fitzpatrick skin types I-III. Only 12% were types IV-VI, which increased to almost 30% of the 135 celebrities on the list in 2017 (P = .01). In 1990, just one celebrity (2%) was of mixed race, which increased to 10.4% in 2017.
Among Hispanic women, the changes in attitude are perhaps best captured among younger relative to older patients requesting cosmetic work, according to Maritza I. Perez, MD, professor of dermatology, University of Connecticut, Farmington. She said that her younger patients are less likely to seek rhinoplasty and blepharoplasty relative to her older patients, a reflection perhaps of comfort with their natural looks.
However, “the celebration of Latinas as beautiful, seductive, and sexual is hardly new,” she said, indicating that younger Hispanic patients are probably not driven to modify their ethnic features because they are already widely admired. “Six of the 10 women crowned Miss Universe in the last decade were from Latin American countries,” she noted.
The general willingness of patients within ethnic groups and society as a whole to see ethnic features as admirable and attractive was generally regarded by all the panelists as a positive development.
Dr. Henry, who said she was “encouraged” by such trends as “the natural hair movement” and diminishing interest among her darker patients in lightening skin pigment, said, “I definitely see a change among my patients in regard to their goals.”
For clinicians offering consults to patients seeking cosmetic work, Dr. Henry recommended being aware and sensitive to this evolution in order to offer appropriate care.
Dr. Chiu, emphasizing the pride that many of her patients take in their Asian features, made the same recommendation. She credited globalization and social media for attitudes that have allowed an embrace of what are now far more inclusive standards of beauty.
Dr. Henry reports financial relationships with Allergan and Merz. Dr. Chiu has financial relationships with AbbVie, Cynosure, Merz, Revance, and Solta. Dr. Galadari reports financial relationships with nine pharmaceutical companies, including Allergan, Merz, Revance, and Fillmed Laboratories. Dr. Perez reports no relevant conflicts of interest.
Addressing current standards of beauty at the Skin of Color Update 2021, dermatologists speaking about attitudes within four ethnic groups recounted a similar story: .
This change is relevant to dermatologists consulting with patients for cosmetic procedures. Four dermatologists who recounted the types of procedures their patients are requesting each reported that more patients are seeking cosmetic enhancements that accentuate rather than modify ethnic features.
Lips in Black, Asian, and Arab ethnic groups are just one example.
“Where several years ago, the conversation was really about lip reductions – how we can deemphasize the lip – I am now seeing lots of women of color coming in to ask about lip augmentation, looking to highlight their lips as a point of beauty,” reported Michelle Henry, MD, a dermatologist who practices in New York City.
She is not alone. Others participating on the same panel spoke of a growing interest among their patients to maintain or even emphasize the same ethnic features – including but not limited to lip shape and size that they were once anxious to modify.
In Asian patients, “the goal is not to Westernize,” agreed Annie Chiu, MD, a dermatologist who practices in North Redondo Beach, Calif. For lips, she spoke of the “50-50 ratio” of upper and lower lip symmetry that is consistent with a traditional Asian characteristic.
Like Dr. Henry, Dr. Chiu said that many requests for cosmetic work now involve accentuating Asian features, such as the oval shape of the face, rather than steps to modify this shape. This is a relatively recent change.
“I am finding that more of my patients want to improve the esthetic balance to optimize the appearance within their own ethnicity,” she said.
In the United Arab Emirates (UAE), Hassan Galadari, MD, an American-trained physician who is assistant professor of dermatology at the UAE University in Dubai, recently conducted a poll of his patients. In order of importance, full lips came after wide eyes, a straight nose, and a sharp jaw line. Full cheeks and a round face completed a list that diverges from the California-blond prototype.
Although Angelina Jolie was selected over several Lebanese actresses as a first choice for an icon of beauty in this same poll, Dr. Galadari pointed out that this actress has many of the features, including wide eyes, a straight nose, and full lips, that are consistent with traditional features of Arab beauty.
Perceptions of beauty are not just changing within ethnic groups but reflected in mass culture. Dr. Henry pointed to a published comparison of the “World’s Most Beautiful” list from People magazine in 2017 relative to 1990. Of the 50 celebrities on the list in 1990, 88% were Fitzpatrick skin types I-III. Only 12% were types IV-VI, which increased to almost 30% of the 135 celebrities on the list in 2017 (P = .01). In 1990, just one celebrity (2%) was of mixed race, which increased to 10.4% in 2017.
Among Hispanic women, the changes in attitude are perhaps best captured among younger relative to older patients requesting cosmetic work, according to Maritza I. Perez, MD, professor of dermatology, University of Connecticut, Farmington. She said that her younger patients are less likely to seek rhinoplasty and blepharoplasty relative to her older patients, a reflection perhaps of comfort with their natural looks.
However, “the celebration of Latinas as beautiful, seductive, and sexual is hardly new,” she said, indicating that younger Hispanic patients are probably not driven to modify their ethnic features because they are already widely admired. “Six of the 10 women crowned Miss Universe in the last decade were from Latin American countries,” she noted.
The general willingness of patients within ethnic groups and society as a whole to see ethnic features as admirable and attractive was generally regarded by all the panelists as a positive development.
Dr. Henry, who said she was “encouraged” by such trends as “the natural hair movement” and diminishing interest among her darker patients in lightening skin pigment, said, “I definitely see a change among my patients in regard to their goals.”
For clinicians offering consults to patients seeking cosmetic work, Dr. Henry recommended being aware and sensitive to this evolution in order to offer appropriate care.
Dr. Chiu, emphasizing the pride that many of her patients take in their Asian features, made the same recommendation. She credited globalization and social media for attitudes that have allowed an embrace of what are now far more inclusive standards of beauty.
Dr. Henry reports financial relationships with Allergan and Merz. Dr. Chiu has financial relationships with AbbVie, Cynosure, Merz, Revance, and Solta. Dr. Galadari reports financial relationships with nine pharmaceutical companies, including Allergan, Merz, Revance, and Fillmed Laboratories. Dr. Perez reports no relevant conflicts of interest.
FROM SOC 2021
Growing proportion of cardiac arrests in U.S. considered opioid related
Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.
“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.
The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).
The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
Mortality from opioid-associated cardiac arrest is lower
These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.
When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.
While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.
Rate of opioid-associated cardiac arrests underestimated
In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.
For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.
In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.
In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
Patterns of opioid-induced cardiac arrests evolving
The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.
Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.
“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.
He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.
“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.
In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.
Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.
Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.
Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.
“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.
The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).
The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
Mortality from opioid-associated cardiac arrest is lower
These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.
When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.
While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.
Rate of opioid-associated cardiac arrests underestimated
In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.
For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.
In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.
In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
Patterns of opioid-induced cardiac arrests evolving
The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.
Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.
“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.
He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.
“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.
In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.
Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.
Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.
Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.
“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.
The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).
The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
Mortality from opioid-associated cardiac arrest is lower
These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.
When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.
While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.
Rate of opioid-associated cardiac arrests underestimated
In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.
For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.
In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.
In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
Patterns of opioid-induced cardiac arrests evolving
The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.
Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.
“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.
He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.
“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.
In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.
Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.
Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.
FROM ESC 2021
COVID-19 linked to rise in suicide-related ED visits among youth
After a steep decline in the first months of the COVID-19 pandemic, youth with suicidal thoughts and behaviors visiting an emergency department (ED) resurged with an overrepresentation among girls and children without a prior psychiatric history, according to a cross-sectional study conducted at Kaiser Permanente Northern California.
The latest findings, published in JAMA Psychiatry, are highly consistent with Centers for Disease Control and Prevention data published a few months earlier in the Morbidity and Mortality Weekly Report that looked at these trends among young people aged 12-25 before and during the pandemic. In addition, the new data suggest that prevention efforts might be particularly helpful for these young people and their families.
“As suicide-related encounters have made up more ED volume during the pandemic, increasing ED-based interventions, staff trained in addressing emergency mental health needs, and aftercare resources may also be valuable in addressing the needs of this population,” wrote Kathryn K. Erickson-Ridout, MD, PhD, first author of the more recent study and an adjunct investigator with the Kaiser Permanente Division of Research, Oakland, Calif.
“While these results suggest many of our youth are coping well through the pandemic, we need to be vigilant as health care workers,” she said in an interview.
Dr. Ridout and associates evaluated suicide-related ED visits among children aged 5-17 years presenting to EDs in the Kaiser Permanente Northern California system. Four periods in 2020 were compared with the same four periods in 2019.
In the first period, March through May 2020, the incidence rate ratio (IRR) of suicide-related ED visits among children and adolescents fell more than 40% (IRR, 0.53; P < .001) relative to the same months in 2019. This is consistent with a broader decline in other types of ED visits during the beginning of the COVID-19 pandemic.
In the periods of June through August and September to Dec. 15, suicide-related ED visits increased, reaching prepandemic levels overall but with differences between genders. In girls, an increase in the first period reached significance (IRR, 1.19; P = .04) and then climbed even higher in the second (hazard ratio, 1.22; P < .001).
Youth present with no prior psychiatric history
Among boys, the increase relative to 2019 in the first period was modest and nonsignificant (IRR, 1.05; P = .26) In the second period, suicide-related ED visits fell and the difference relative to the same period in 2019 reached statistical significance (IRR, 0.81; P = .02).
Other characteristics of suicide-related ED visits during the pandemic were also different from those observed in 2019. One was an increase in visits from youth with no prior history of mental health or suicide-related outpatient visits.
“This finding may suggest that a youth’s first presentation to the ED for suicidal thoughts and behaviors differed during the pandemic, compared to prior to the pandemic,” Dr. Erickson-Ridout explained. “Mental health comorbidities first diagnosed at the ED encounter may suggest an increased complexity at first presentation.”
These data are remarkably similar to ED visits for suicide attempts that were reported by the CDC several months earlier. The CDC data were drawn from the National Syndromic Surveillance Program, which captures data from 71% of the EDs in the United States.
Measured from March 29 to April 25, 2020, ED visits for a suicide attempt declined by more than 25% in both girls and boys, but by early May, those visits were already starting to return to prepandemic levels, particularly among girls, according to the CDC report. When evaluated from July 26 through Aug. 22, 2020, the mean weekly ED visits for suspected suicide attempts had increased 26.2% among girls but only 10.8% among boys, compared with the same period in 2019.
‘More severe distress’ found among girls
In the most recent period evaluated, starting Feb. 21, 2021, and extending to March 20, , compared with the same period in 2019. For boys, the increase was 3.7%.
Higher rates of suicide attempts among girls have been reported by others independent of the COVID-19 pandemic, but the CDC investigators led by Ellen Yard, PhD, a researcher in the CDC’s National Center for Environmental Health, Chamblee, Ga., reported that others have also found greater suicide ideation and attempts by girls during the pandemic.
Neither study was designed to isolate the reason or reasons for an increase in suicide-related ED visits overall or among girls specifically, but Dr. Yard and her coinvestigators speculated that social distancing and isolation during the COVID-19 pandemic might be affecting girls more.
The faster increase in suicide attempts among girls compared with boys “speaks to the importance of upstream prevention to prevent this group from becoming suicidal in the first place as well as improving suicide care both during and after ED visits,” said Dr. Yard, who was interviewed about this research.
For clinicians, she recommended “scaling up adoption of evidence-based best practice.” She cited two such resources from the National Action Alliance for Suicide Prevention (NAASP). One resource is the Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care; the other is called Recommended Standard Care. Both are available online for free from the NAASP.
Dr. Erickson-Ridout and Dr. Yard reported no potential conflicts of interest.
After a steep decline in the first months of the COVID-19 pandemic, youth with suicidal thoughts and behaviors visiting an emergency department (ED) resurged with an overrepresentation among girls and children without a prior psychiatric history, according to a cross-sectional study conducted at Kaiser Permanente Northern California.
The latest findings, published in JAMA Psychiatry, are highly consistent with Centers for Disease Control and Prevention data published a few months earlier in the Morbidity and Mortality Weekly Report that looked at these trends among young people aged 12-25 before and during the pandemic. In addition, the new data suggest that prevention efforts might be particularly helpful for these young people and their families.
“As suicide-related encounters have made up more ED volume during the pandemic, increasing ED-based interventions, staff trained in addressing emergency mental health needs, and aftercare resources may also be valuable in addressing the needs of this population,” wrote Kathryn K. Erickson-Ridout, MD, PhD, first author of the more recent study and an adjunct investigator with the Kaiser Permanente Division of Research, Oakland, Calif.
“While these results suggest many of our youth are coping well through the pandemic, we need to be vigilant as health care workers,” she said in an interview.
Dr. Ridout and associates evaluated suicide-related ED visits among children aged 5-17 years presenting to EDs in the Kaiser Permanente Northern California system. Four periods in 2020 were compared with the same four periods in 2019.
In the first period, March through May 2020, the incidence rate ratio (IRR) of suicide-related ED visits among children and adolescents fell more than 40% (IRR, 0.53; P < .001) relative to the same months in 2019. This is consistent with a broader decline in other types of ED visits during the beginning of the COVID-19 pandemic.
In the periods of June through August and September to Dec. 15, suicide-related ED visits increased, reaching prepandemic levels overall but with differences between genders. In girls, an increase in the first period reached significance (IRR, 1.19; P = .04) and then climbed even higher in the second (hazard ratio, 1.22; P < .001).
Youth present with no prior psychiatric history
Among boys, the increase relative to 2019 in the first period was modest and nonsignificant (IRR, 1.05; P = .26) In the second period, suicide-related ED visits fell and the difference relative to the same period in 2019 reached statistical significance (IRR, 0.81; P = .02).
Other characteristics of suicide-related ED visits during the pandemic were also different from those observed in 2019. One was an increase in visits from youth with no prior history of mental health or suicide-related outpatient visits.
“This finding may suggest that a youth’s first presentation to the ED for suicidal thoughts and behaviors differed during the pandemic, compared to prior to the pandemic,” Dr. Erickson-Ridout explained. “Mental health comorbidities first diagnosed at the ED encounter may suggest an increased complexity at first presentation.”
These data are remarkably similar to ED visits for suicide attempts that were reported by the CDC several months earlier. The CDC data were drawn from the National Syndromic Surveillance Program, which captures data from 71% of the EDs in the United States.
Measured from March 29 to April 25, 2020, ED visits for a suicide attempt declined by more than 25% in both girls and boys, but by early May, those visits were already starting to return to prepandemic levels, particularly among girls, according to the CDC report. When evaluated from July 26 through Aug. 22, 2020, the mean weekly ED visits for suspected suicide attempts had increased 26.2% among girls but only 10.8% among boys, compared with the same period in 2019.
‘More severe distress’ found among girls
In the most recent period evaluated, starting Feb. 21, 2021, and extending to March 20, , compared with the same period in 2019. For boys, the increase was 3.7%.
Higher rates of suicide attempts among girls have been reported by others independent of the COVID-19 pandemic, but the CDC investigators led by Ellen Yard, PhD, a researcher in the CDC’s National Center for Environmental Health, Chamblee, Ga., reported that others have also found greater suicide ideation and attempts by girls during the pandemic.
Neither study was designed to isolate the reason or reasons for an increase in suicide-related ED visits overall or among girls specifically, but Dr. Yard and her coinvestigators speculated that social distancing and isolation during the COVID-19 pandemic might be affecting girls more.
The faster increase in suicide attempts among girls compared with boys “speaks to the importance of upstream prevention to prevent this group from becoming suicidal in the first place as well as improving suicide care both during and after ED visits,” said Dr. Yard, who was interviewed about this research.
For clinicians, she recommended “scaling up adoption of evidence-based best practice.” She cited two such resources from the National Action Alliance for Suicide Prevention (NAASP). One resource is the Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care; the other is called Recommended Standard Care. Both are available online for free from the NAASP.
Dr. Erickson-Ridout and Dr. Yard reported no potential conflicts of interest.
After a steep decline in the first months of the COVID-19 pandemic, youth with suicidal thoughts and behaviors visiting an emergency department (ED) resurged with an overrepresentation among girls and children without a prior psychiatric history, according to a cross-sectional study conducted at Kaiser Permanente Northern California.
The latest findings, published in JAMA Psychiatry, are highly consistent with Centers for Disease Control and Prevention data published a few months earlier in the Morbidity and Mortality Weekly Report that looked at these trends among young people aged 12-25 before and during the pandemic. In addition, the new data suggest that prevention efforts might be particularly helpful for these young people and their families.
“As suicide-related encounters have made up more ED volume during the pandemic, increasing ED-based interventions, staff trained in addressing emergency mental health needs, and aftercare resources may also be valuable in addressing the needs of this population,” wrote Kathryn K. Erickson-Ridout, MD, PhD, first author of the more recent study and an adjunct investigator with the Kaiser Permanente Division of Research, Oakland, Calif.
“While these results suggest many of our youth are coping well through the pandemic, we need to be vigilant as health care workers,” she said in an interview.
Dr. Ridout and associates evaluated suicide-related ED visits among children aged 5-17 years presenting to EDs in the Kaiser Permanente Northern California system. Four periods in 2020 were compared with the same four periods in 2019.
In the first period, March through May 2020, the incidence rate ratio (IRR) of suicide-related ED visits among children and adolescents fell more than 40% (IRR, 0.53; P < .001) relative to the same months in 2019. This is consistent with a broader decline in other types of ED visits during the beginning of the COVID-19 pandemic.
In the periods of June through August and September to Dec. 15, suicide-related ED visits increased, reaching prepandemic levels overall but with differences between genders. In girls, an increase in the first period reached significance (IRR, 1.19; P = .04) and then climbed even higher in the second (hazard ratio, 1.22; P < .001).
Youth present with no prior psychiatric history
Among boys, the increase relative to 2019 in the first period was modest and nonsignificant (IRR, 1.05; P = .26) In the second period, suicide-related ED visits fell and the difference relative to the same period in 2019 reached statistical significance (IRR, 0.81; P = .02).
Other characteristics of suicide-related ED visits during the pandemic were also different from those observed in 2019. One was an increase in visits from youth with no prior history of mental health or suicide-related outpatient visits.
“This finding may suggest that a youth’s first presentation to the ED for suicidal thoughts and behaviors differed during the pandemic, compared to prior to the pandemic,” Dr. Erickson-Ridout explained. “Mental health comorbidities first diagnosed at the ED encounter may suggest an increased complexity at first presentation.”
These data are remarkably similar to ED visits for suicide attempts that were reported by the CDC several months earlier. The CDC data were drawn from the National Syndromic Surveillance Program, which captures data from 71% of the EDs in the United States.
Measured from March 29 to April 25, 2020, ED visits for a suicide attempt declined by more than 25% in both girls and boys, but by early May, those visits were already starting to return to prepandemic levels, particularly among girls, according to the CDC report. When evaluated from July 26 through Aug. 22, 2020, the mean weekly ED visits for suspected suicide attempts had increased 26.2% among girls but only 10.8% among boys, compared with the same period in 2019.
‘More severe distress’ found among girls
In the most recent period evaluated, starting Feb. 21, 2021, and extending to March 20, , compared with the same period in 2019. For boys, the increase was 3.7%.
Higher rates of suicide attempts among girls have been reported by others independent of the COVID-19 pandemic, but the CDC investigators led by Ellen Yard, PhD, a researcher in the CDC’s National Center for Environmental Health, Chamblee, Ga., reported that others have also found greater suicide ideation and attempts by girls during the pandemic.
Neither study was designed to isolate the reason or reasons for an increase in suicide-related ED visits overall or among girls specifically, but Dr. Yard and her coinvestigators speculated that social distancing and isolation during the COVID-19 pandemic might be affecting girls more.
The faster increase in suicide attempts among girls compared with boys “speaks to the importance of upstream prevention to prevent this group from becoming suicidal in the first place as well as improving suicide care both during and after ED visits,” said Dr. Yard, who was interviewed about this research.
For clinicians, she recommended “scaling up adoption of evidence-based best practice.” She cited two such resources from the National Action Alliance for Suicide Prevention (NAASP). One resource is the Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care; the other is called Recommended Standard Care. Both are available online for free from the NAASP.
Dr. Erickson-Ridout and Dr. Yard reported no potential conflicts of interest.
FROM JAMA PSYCHIATRY
Atopic dermatitis doubles risk of mental health issues in children
, according to a newly published cohort study of more than 11,000 children between the ages of 3 and 18 years.
Along with previous studies that have also linked AD to depression and other mental health issues in children, these data highlight the need for “clinical awareness of the psychosocial needs of children and adolescents with AD,” reported a multicenter team of investigators from the University of California, San Francisco, the University of Pennsylvania, and the London School of Hygiene and Tropical Medicine.
Unlike some previous studies, in this study, published online in JAMA Dermatology on Sept. 1, children were evaluated longitudinally, rather than at a single point in time, with a mean follow-up of 10 years. For those with active AD, compared with children without AD, the odds ratio for depression overall in any child with AD relative to those without AD was not significant after adjustment for variables such socioeconomic factors.
However, among children with severe AD, the risk was more than twofold greater even after adjustment (adjusted OR, 2.38; 95% confidence interval, 1.21- 4.72), reported the investigators, led by senior author Katrina Abuabara, MD, associate professor of dermatology and epidemiology at UCSF.
Internalizing symptoms seen with mild to severe AD
Internalizing behavior, which is closely linked to depression and describes a spectrum of inward-focusing activities, such as social withdrawal, was significantly more common in children with any degree of AD relative to those without AD: After adjustment, the risk climbed from a 29% increased risk in those with mild AD (aOR, 1.29; 95% CI, 1.06-1.57) to a more than 80% increased risk in children with moderate AD (aOR, 1.84; 95% CI, 1.40-2.41) and in children with severe AD (aOR, 1.90; 95% CI, 1.14-3.16).
In the study, depression was measured with the Short Moods and Feelings Questionnaire (SMFQ). Parental response to the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire (SDQ) was used to measure internalizing behaviors.
The data were drawn from the Avon Longitudinal Study for Parents and Children (ALSPAC), a cohort that enrolled pregnant women in a defined area in southwest England and then followed children born from these pregnancies. Of the 14,062 children enrolled in ALSPAC, data from 11,181 children were available for this study.
In a previous meta-analysis of studies that have documented a link between AD and adverse effects on mood and mental health, an impact was identified in both children and adults. In children, AD was associated with a 27% increase in risk of depression (OR, 1.27; 95% CI, 1.12 -1.45). In adults, the risk was more than doubled (OR, 2.19; 95% CI, 1.87-2.57). The same meta-analysis found that the risk of suicidal ideation among adolescents and adults with AD was increased more than fourfold (OR, 4.32; 95% CI, 1.93-9.66).
In the ALSPAC data, the investigators were unable to find compelling evidence that sleep disturbances or concomitant asthma contributed to the increased risk of depression, which is a mechanism proposed by past investigators.
In an interview, Dr. Abuabara said that these and other data provide the basis for encouraging clinical awareness of the psychological needs of children with AD, but she suggested there is a gap in understanding what this means clinically. “We need more data on how dermatologists can effectively screen and manage these patients before we try to set expectations for clinical practice,” she said.
In addition, these data along with previously published studies suggest that change in mental health outcomes should be included in the evaluation of new therapies, according to Dr. Abuabara. She noted that there are several tools for evaluating mental health in children that might be appropriate, each with their own advantages and disadvantages.
“Ideally, recommendations would be issued through a group consensus process with patients, clinicians, researchers, and industry representatives working together as has been done for other outcomes through the Harmonizing Measures for Eczema (HOME) group,” Dr. Abuabara said.
Mental health assessments recommended
Others who have looked at the relationship between AD and depression have also recommended adding mental health outcomes to an assessment of efficacy for AD therapies.
Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, is one such investigator. He is already monitoring depression systematically with the Hospital Anxiety and Depression Scale (HADS).
“HADS has been validated in AD and provides very important information about the emotional burden of AD,” explained Dr. Silverberg, whose most recent article on this topic appeared earlier this year. In that study, the relationship between AD and depression was found to be more pronounced in White children from families with lower incomes.
“Just a few hours ago, one of my patients thanked me for asking about their mental health and recognizing the holistic effects of AD,” Dr. Silverberg said.
The recent study based on ALSPAC data add to the evidence that AD, particularly severe AD, produces deleterious effects on mental health in children, and Dr. Silverberg believes clinicians should be acting on this evidence.
“I strongly encourage clinicians to routinely assess mental health. It will elevate the quality of care they provide, and their patients will appreciate them more for it,” he said.
Dr. Abuabara and another author report receiving research funding from Pfizer to their universities for unrelated work; there were no other disclosures. Dr. Silverberg reports financial relationships with more than 15 pharmaceutical companies.
Commentary by Lawrence F. Eichenfield, MD
More severe atopic dermatitis (AD) carries with it significant mental health concerns in children, as well as adults. Multiple studies have shown significantly higher rates of depression, anxiety, and “internalizing behaviors” (discussed as social withdrawal and other inward-focused activities) as well as attention-deficit/hyperactivity disorder. The study by Dr. Abuabara and colleagues is important as it followed children over time (an average of 10 years) and adjusted the data for socioeconomic factors, showing a rate of depression in children with severe AD twice that of those without. It appears that we are in the midst of a mental health crisis in children and teens, with markedly higher rates of pediatric and adolescent depression and anxiety, certainly influenced by COVID-19 societal changes. As the literature has developed on depression and AD, we have appreciated the importance of addressing this as part of our assessment of the disease effect on the individual and family, and it is one factor we consider in selections of systemic vs. topical therapies.
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.
A version of this article first appeared on Medscape.com.
This article was updated 6/18/22.
, according to a newly published cohort study of more than 11,000 children between the ages of 3 and 18 years.
Along with previous studies that have also linked AD to depression and other mental health issues in children, these data highlight the need for “clinical awareness of the psychosocial needs of children and adolescents with AD,” reported a multicenter team of investigators from the University of California, San Francisco, the University of Pennsylvania, and the London School of Hygiene and Tropical Medicine.
Unlike some previous studies, in this study, published online in JAMA Dermatology on Sept. 1, children were evaluated longitudinally, rather than at a single point in time, with a mean follow-up of 10 years. For those with active AD, compared with children without AD, the odds ratio for depression overall in any child with AD relative to those without AD was not significant after adjustment for variables such socioeconomic factors.
However, among children with severe AD, the risk was more than twofold greater even after adjustment (adjusted OR, 2.38; 95% confidence interval, 1.21- 4.72), reported the investigators, led by senior author Katrina Abuabara, MD, associate professor of dermatology and epidemiology at UCSF.
Internalizing symptoms seen with mild to severe AD
Internalizing behavior, which is closely linked to depression and describes a spectrum of inward-focusing activities, such as social withdrawal, was significantly more common in children with any degree of AD relative to those without AD: After adjustment, the risk climbed from a 29% increased risk in those with mild AD (aOR, 1.29; 95% CI, 1.06-1.57) to a more than 80% increased risk in children with moderate AD (aOR, 1.84; 95% CI, 1.40-2.41) and in children with severe AD (aOR, 1.90; 95% CI, 1.14-3.16).
In the study, depression was measured with the Short Moods and Feelings Questionnaire (SMFQ). Parental response to the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire (SDQ) was used to measure internalizing behaviors.
The data were drawn from the Avon Longitudinal Study for Parents and Children (ALSPAC), a cohort that enrolled pregnant women in a defined area in southwest England and then followed children born from these pregnancies. Of the 14,062 children enrolled in ALSPAC, data from 11,181 children were available for this study.
In a previous meta-analysis of studies that have documented a link between AD and adverse effects on mood and mental health, an impact was identified in both children and adults. In children, AD was associated with a 27% increase in risk of depression (OR, 1.27; 95% CI, 1.12 -1.45). In adults, the risk was more than doubled (OR, 2.19; 95% CI, 1.87-2.57). The same meta-analysis found that the risk of suicidal ideation among adolescents and adults with AD was increased more than fourfold (OR, 4.32; 95% CI, 1.93-9.66).
In the ALSPAC data, the investigators were unable to find compelling evidence that sleep disturbances or concomitant asthma contributed to the increased risk of depression, which is a mechanism proposed by past investigators.
In an interview, Dr. Abuabara said that these and other data provide the basis for encouraging clinical awareness of the psychological needs of children with AD, but she suggested there is a gap in understanding what this means clinically. “We need more data on how dermatologists can effectively screen and manage these patients before we try to set expectations for clinical practice,” she said.
In addition, these data along with previously published studies suggest that change in mental health outcomes should be included in the evaluation of new therapies, according to Dr. Abuabara. She noted that there are several tools for evaluating mental health in children that might be appropriate, each with their own advantages and disadvantages.
“Ideally, recommendations would be issued through a group consensus process with patients, clinicians, researchers, and industry representatives working together as has been done for other outcomes through the Harmonizing Measures for Eczema (HOME) group,” Dr. Abuabara said.
Mental health assessments recommended
Others who have looked at the relationship between AD and depression have also recommended adding mental health outcomes to an assessment of efficacy for AD therapies.
Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, is one such investigator. He is already monitoring depression systematically with the Hospital Anxiety and Depression Scale (HADS).
“HADS has been validated in AD and provides very important information about the emotional burden of AD,” explained Dr. Silverberg, whose most recent article on this topic appeared earlier this year. In that study, the relationship between AD and depression was found to be more pronounced in White children from families with lower incomes.
“Just a few hours ago, one of my patients thanked me for asking about their mental health and recognizing the holistic effects of AD,” Dr. Silverberg said.
The recent study based on ALSPAC data add to the evidence that AD, particularly severe AD, produces deleterious effects on mental health in children, and Dr. Silverberg believes clinicians should be acting on this evidence.
“I strongly encourage clinicians to routinely assess mental health. It will elevate the quality of care they provide, and their patients will appreciate them more for it,” he said.
Dr. Abuabara and another author report receiving research funding from Pfizer to their universities for unrelated work; there were no other disclosures. Dr. Silverberg reports financial relationships with more than 15 pharmaceutical companies.
Commentary by Lawrence F. Eichenfield, MD
More severe atopic dermatitis (AD) carries with it significant mental health concerns in children, as well as adults. Multiple studies have shown significantly higher rates of depression, anxiety, and “internalizing behaviors” (discussed as social withdrawal and other inward-focused activities) as well as attention-deficit/hyperactivity disorder. The study by Dr. Abuabara and colleagues is important as it followed children over time (an average of 10 years) and adjusted the data for socioeconomic factors, showing a rate of depression in children with severe AD twice that of those without. It appears that we are in the midst of a mental health crisis in children and teens, with markedly higher rates of pediatric and adolescent depression and anxiety, certainly influenced by COVID-19 societal changes. As the literature has developed on depression and AD, we have appreciated the importance of addressing this as part of our assessment of the disease effect on the individual and family, and it is one factor we consider in selections of systemic vs. topical therapies.
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.
A version of this article first appeared on Medscape.com.
This article was updated 6/18/22.
, according to a newly published cohort study of more than 11,000 children between the ages of 3 and 18 years.
Along with previous studies that have also linked AD to depression and other mental health issues in children, these data highlight the need for “clinical awareness of the psychosocial needs of children and adolescents with AD,” reported a multicenter team of investigators from the University of California, San Francisco, the University of Pennsylvania, and the London School of Hygiene and Tropical Medicine.
Unlike some previous studies, in this study, published online in JAMA Dermatology on Sept. 1, children were evaluated longitudinally, rather than at a single point in time, with a mean follow-up of 10 years. For those with active AD, compared with children without AD, the odds ratio for depression overall in any child with AD relative to those without AD was not significant after adjustment for variables such socioeconomic factors.
However, among children with severe AD, the risk was more than twofold greater even after adjustment (adjusted OR, 2.38; 95% confidence interval, 1.21- 4.72), reported the investigators, led by senior author Katrina Abuabara, MD, associate professor of dermatology and epidemiology at UCSF.
Internalizing symptoms seen with mild to severe AD
Internalizing behavior, which is closely linked to depression and describes a spectrum of inward-focusing activities, such as social withdrawal, was significantly more common in children with any degree of AD relative to those without AD: After adjustment, the risk climbed from a 29% increased risk in those with mild AD (aOR, 1.29; 95% CI, 1.06-1.57) to a more than 80% increased risk in children with moderate AD (aOR, 1.84; 95% CI, 1.40-2.41) and in children with severe AD (aOR, 1.90; 95% CI, 1.14-3.16).
In the study, depression was measured with the Short Moods and Feelings Questionnaire (SMFQ). Parental response to the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire (SDQ) was used to measure internalizing behaviors.
The data were drawn from the Avon Longitudinal Study for Parents and Children (ALSPAC), a cohort that enrolled pregnant women in a defined area in southwest England and then followed children born from these pregnancies. Of the 14,062 children enrolled in ALSPAC, data from 11,181 children were available for this study.
In a previous meta-analysis of studies that have documented a link between AD and adverse effects on mood and mental health, an impact was identified in both children and adults. In children, AD was associated with a 27% increase in risk of depression (OR, 1.27; 95% CI, 1.12 -1.45). In adults, the risk was more than doubled (OR, 2.19; 95% CI, 1.87-2.57). The same meta-analysis found that the risk of suicidal ideation among adolescents and adults with AD was increased more than fourfold (OR, 4.32; 95% CI, 1.93-9.66).
In the ALSPAC data, the investigators were unable to find compelling evidence that sleep disturbances or concomitant asthma contributed to the increased risk of depression, which is a mechanism proposed by past investigators.
In an interview, Dr. Abuabara said that these and other data provide the basis for encouraging clinical awareness of the psychological needs of children with AD, but she suggested there is a gap in understanding what this means clinically. “We need more data on how dermatologists can effectively screen and manage these patients before we try to set expectations for clinical practice,” she said.
In addition, these data along with previously published studies suggest that change in mental health outcomes should be included in the evaluation of new therapies, according to Dr. Abuabara. She noted that there are several tools for evaluating mental health in children that might be appropriate, each with their own advantages and disadvantages.
“Ideally, recommendations would be issued through a group consensus process with patients, clinicians, researchers, and industry representatives working together as has been done for other outcomes through the Harmonizing Measures for Eczema (HOME) group,” Dr. Abuabara said.
Mental health assessments recommended
Others who have looked at the relationship between AD and depression have also recommended adding mental health outcomes to an assessment of efficacy for AD therapies.
Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, is one such investigator. He is already monitoring depression systematically with the Hospital Anxiety and Depression Scale (HADS).
“HADS has been validated in AD and provides very important information about the emotional burden of AD,” explained Dr. Silverberg, whose most recent article on this topic appeared earlier this year. In that study, the relationship between AD and depression was found to be more pronounced in White children from families with lower incomes.
“Just a few hours ago, one of my patients thanked me for asking about their mental health and recognizing the holistic effects of AD,” Dr. Silverberg said.
The recent study based on ALSPAC data add to the evidence that AD, particularly severe AD, produces deleterious effects on mental health in children, and Dr. Silverberg believes clinicians should be acting on this evidence.
“I strongly encourage clinicians to routinely assess mental health. It will elevate the quality of care they provide, and their patients will appreciate them more for it,” he said.
Dr. Abuabara and another author report receiving research funding from Pfizer to their universities for unrelated work; there were no other disclosures. Dr. Silverberg reports financial relationships with more than 15 pharmaceutical companies.
Commentary by Lawrence F. Eichenfield, MD
More severe atopic dermatitis (AD) carries with it significant mental health concerns in children, as well as adults. Multiple studies have shown significantly higher rates of depression, anxiety, and “internalizing behaviors” (discussed as social withdrawal and other inward-focused activities) as well as attention-deficit/hyperactivity disorder. The study by Dr. Abuabara and colleagues is important as it followed children over time (an average of 10 years) and adjusted the data for socioeconomic factors, showing a rate of depression in children with severe AD twice that of those without. It appears that we are in the midst of a mental health crisis in children and teens, with markedly higher rates of pediatric and adolescent depression and anxiety, certainly influenced by COVID-19 societal changes. As the literature has developed on depression and AD, we have appreciated the importance of addressing this as part of our assessment of the disease effect on the individual and family, and it is one factor we consider in selections of systemic vs. topical therapies.
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.
A version of this article first appeared on Medscape.com.
This article was updated 6/18/22.
FROM JAMA DERMATOLOGY
New valvular heart disease guidelines change several repair indications
Antithrombotic recommendations also altered
New European guidelines for the management of valvular heart disease offer more than 45 revised or completely new recommendations relative to the previous version published in 2017, according to members of the writing committee who presented the changes during the annual congress of the European Society of Cardiology.
With their emphasis on early diagnosis and expansion of indications, these 2021 ESC/European Association for Cardio-Thoracic Surgery guidelines are likely to further accelerate the already steep growth in this area of interventional cardiology, according to Alec Vahanian, MD, a professor of cardiology at the University of Paris.
“Valvular heart disease is too often undetected, and these guidelines stress the importance of clinical examination and the best strategies for diagnosis as well as treatment,” he said.
Of the multiple sections and subsections, which follow the same format of the previous guidelines, the greatest number of revisions and new additions involve perioperative antithrombotic therapy, according to the document, which was published in conjunction with the ESC Congress.
Eleven new guidelines for anticoagulants
On the basis of evidence published since the previous guidelines, there are 11 completely new recommendations regarding the use of anticoagulants or antiplatelet therapies. The majority of these have received a grade I indication, which signifies “recommended” or “indicated.” These include indications for stopping or starting anticoagulants and which anticoagulants or antiplatelet drugs to consider in specific patient populations.
The next most common focus of new or revised recommendations involves when to consider surgical aortic valve repair (SAVR) relative to transcatheter aortic valve implantation (TAVI) in severe aortic stenosis. Most of these represent revisions from the previous guidelines, but almost all are also grade I recommendations.
“SAVR and TAVI are both excellent options in appropriate patients, but they are not interchangeable,” explained Bernard D. Prendergast, BMedSci, MD, director of the cardiac structural intervention program, Guy’s and St Thomas’ Hospital, London.
While the previous guidelines generally reserved TAVI for those not suitable for SAVR, the new guidelines are more nuanced.
As a rule, SAVR is generally preferred for younger patients. The reason, according to Dr. Prendergast, is concern that younger patients might outlive the expected lifespan of the prosthetic TAVI device.
No single criterion for selecting SAVR over TAVI
However, there are many exceptions and additional considerations beyond age. When both SAVR and TAVI are otherwise suitable options, but TAVI cannot be performed with a transfemoral access, Dr. Prendergast pointed out that SAVR might be a better choice.
Transfemoral access is the preferred strategy in TAVI, but Dr. Prendergast emphasized that a collaborative “heart team” should help patients select the most appropriate option. In fact, there is a grade IIb recommendation (“usefulness or efficacy is less well established”) to consider other access sites in patients at high surgical risk with contraindications for transfemoral TAVI.
Of new recommendations in the area of severe aortic stenosis, valvular repair may now be considered in asymptomatic patients with a left ventricular ejection fraction of less than 55%, according to a grade IIb recommendation. The 2017 guidelines did not address this issue.
Grade I recommendation for bioprostheses
A substantial number of the revisions involve minor clarifications without a change in the grade, but a revision regarding bioprosthetics is substantial. In the 2017 guidelines, there was a grade IIa recommendation (“weight of evidence is in favor”) to consider bioprosthetics in patients with a life expectancy less than the expected durability of the device. The 2021 guidelines have changed this to a grade I indication, adding an indication for bioprostheses in patients contraindicated for or unlikely to achieve good-quality anticoagulation.
On this same topic, there is a new grade IIb recommendation to consider bioprosthesis over alternative devices in patients already on a long-term non–vitamin K oral anticoagulant because of the high risk of thromboembolism.
There are two new recommendations in the realm of severe secondary mitral regurgitation, reported Fabien Praz, MD, an interventional cardiologist at the University of Bern (Switzerland). The first, which is perhaps the most significant, is a grade I recommendation for valve surgery in patients with severe secondary mitral regurgitation who remain symptomatic despite optimized medical therapy.
The second is a grade IIa recommendation for invasive procedures, such as a percutaneous coronary intervention, for patients with symptomatic secondary mitral regurgitation and coexisting coronary artery disease. In both cases, however, Dr. Praz emphasized language in the guidelines that calls for a collaborative heart team to agree on the suitability of these treatments.
Ultimately, none of these recommendations can be divorced from patient expectations and values, according to Friedhelm Beyersdorf, MD, chairman of the department of cardiovascular surgery at the Heart Center of the University of Freiburg (Germany).
Even if treatment is not expected to prolong life, “symptom relief on its own may justify intervention,” said Dr. Beyersdorf. However, he emphasized that “thoroughly informed” patients are an essential part of the process in selecting a treatment strategy most likely to satisfy patient goals.
Dr. Vahanian and Dr. Prendergast reported no conflicts of interest relevant to these guidelines. Dr. Praz reported a financial relationship with Edwards Lifesciences. Dr. Beyersdorf reported a financial relationship with Resuscitec.
Antithrombotic recommendations also altered
Antithrombotic recommendations also altered
New European guidelines for the management of valvular heart disease offer more than 45 revised or completely new recommendations relative to the previous version published in 2017, according to members of the writing committee who presented the changes during the annual congress of the European Society of Cardiology.
With their emphasis on early diagnosis and expansion of indications, these 2021 ESC/European Association for Cardio-Thoracic Surgery guidelines are likely to further accelerate the already steep growth in this area of interventional cardiology, according to Alec Vahanian, MD, a professor of cardiology at the University of Paris.
“Valvular heart disease is too often undetected, and these guidelines stress the importance of clinical examination and the best strategies for diagnosis as well as treatment,” he said.
Of the multiple sections and subsections, which follow the same format of the previous guidelines, the greatest number of revisions and new additions involve perioperative antithrombotic therapy, according to the document, which was published in conjunction with the ESC Congress.
Eleven new guidelines for anticoagulants
On the basis of evidence published since the previous guidelines, there are 11 completely new recommendations regarding the use of anticoagulants or antiplatelet therapies. The majority of these have received a grade I indication, which signifies “recommended” or “indicated.” These include indications for stopping or starting anticoagulants and which anticoagulants or antiplatelet drugs to consider in specific patient populations.
The next most common focus of new or revised recommendations involves when to consider surgical aortic valve repair (SAVR) relative to transcatheter aortic valve implantation (TAVI) in severe aortic stenosis. Most of these represent revisions from the previous guidelines, but almost all are also grade I recommendations.
“SAVR and TAVI are both excellent options in appropriate patients, but they are not interchangeable,” explained Bernard D. Prendergast, BMedSci, MD, director of the cardiac structural intervention program, Guy’s and St Thomas’ Hospital, London.
While the previous guidelines generally reserved TAVI for those not suitable for SAVR, the new guidelines are more nuanced.
As a rule, SAVR is generally preferred for younger patients. The reason, according to Dr. Prendergast, is concern that younger patients might outlive the expected lifespan of the prosthetic TAVI device.
No single criterion for selecting SAVR over TAVI
However, there are many exceptions and additional considerations beyond age. When both SAVR and TAVI are otherwise suitable options, but TAVI cannot be performed with a transfemoral access, Dr. Prendergast pointed out that SAVR might be a better choice.
Transfemoral access is the preferred strategy in TAVI, but Dr. Prendergast emphasized that a collaborative “heart team” should help patients select the most appropriate option. In fact, there is a grade IIb recommendation (“usefulness or efficacy is less well established”) to consider other access sites in patients at high surgical risk with contraindications for transfemoral TAVI.
Of new recommendations in the area of severe aortic stenosis, valvular repair may now be considered in asymptomatic patients with a left ventricular ejection fraction of less than 55%, according to a grade IIb recommendation. The 2017 guidelines did not address this issue.
Grade I recommendation for bioprostheses
A substantial number of the revisions involve minor clarifications without a change in the grade, but a revision regarding bioprosthetics is substantial. In the 2017 guidelines, there was a grade IIa recommendation (“weight of evidence is in favor”) to consider bioprosthetics in patients with a life expectancy less than the expected durability of the device. The 2021 guidelines have changed this to a grade I indication, adding an indication for bioprostheses in patients contraindicated for or unlikely to achieve good-quality anticoagulation.
On this same topic, there is a new grade IIb recommendation to consider bioprosthesis over alternative devices in patients already on a long-term non–vitamin K oral anticoagulant because of the high risk of thromboembolism.
There are two new recommendations in the realm of severe secondary mitral regurgitation, reported Fabien Praz, MD, an interventional cardiologist at the University of Bern (Switzerland). The first, which is perhaps the most significant, is a grade I recommendation for valve surgery in patients with severe secondary mitral regurgitation who remain symptomatic despite optimized medical therapy.
The second is a grade IIa recommendation for invasive procedures, such as a percutaneous coronary intervention, for patients with symptomatic secondary mitral regurgitation and coexisting coronary artery disease. In both cases, however, Dr. Praz emphasized language in the guidelines that calls for a collaborative heart team to agree on the suitability of these treatments.
Ultimately, none of these recommendations can be divorced from patient expectations and values, according to Friedhelm Beyersdorf, MD, chairman of the department of cardiovascular surgery at the Heart Center of the University of Freiburg (Germany).
Even if treatment is not expected to prolong life, “symptom relief on its own may justify intervention,” said Dr. Beyersdorf. However, he emphasized that “thoroughly informed” patients are an essential part of the process in selecting a treatment strategy most likely to satisfy patient goals.
Dr. Vahanian and Dr. Prendergast reported no conflicts of interest relevant to these guidelines. Dr. Praz reported a financial relationship with Edwards Lifesciences. Dr. Beyersdorf reported a financial relationship with Resuscitec.
New European guidelines for the management of valvular heart disease offer more than 45 revised or completely new recommendations relative to the previous version published in 2017, according to members of the writing committee who presented the changes during the annual congress of the European Society of Cardiology.
With their emphasis on early diagnosis and expansion of indications, these 2021 ESC/European Association for Cardio-Thoracic Surgery guidelines are likely to further accelerate the already steep growth in this area of interventional cardiology, according to Alec Vahanian, MD, a professor of cardiology at the University of Paris.
“Valvular heart disease is too often undetected, and these guidelines stress the importance of clinical examination and the best strategies for diagnosis as well as treatment,” he said.
Of the multiple sections and subsections, which follow the same format of the previous guidelines, the greatest number of revisions and new additions involve perioperative antithrombotic therapy, according to the document, which was published in conjunction with the ESC Congress.
Eleven new guidelines for anticoagulants
On the basis of evidence published since the previous guidelines, there are 11 completely new recommendations regarding the use of anticoagulants or antiplatelet therapies. The majority of these have received a grade I indication, which signifies “recommended” or “indicated.” These include indications for stopping or starting anticoagulants and which anticoagulants or antiplatelet drugs to consider in specific patient populations.
The next most common focus of new or revised recommendations involves when to consider surgical aortic valve repair (SAVR) relative to transcatheter aortic valve implantation (TAVI) in severe aortic stenosis. Most of these represent revisions from the previous guidelines, but almost all are also grade I recommendations.
“SAVR and TAVI are both excellent options in appropriate patients, but they are not interchangeable,” explained Bernard D. Prendergast, BMedSci, MD, director of the cardiac structural intervention program, Guy’s and St Thomas’ Hospital, London.
While the previous guidelines generally reserved TAVI for those not suitable for SAVR, the new guidelines are more nuanced.
As a rule, SAVR is generally preferred for younger patients. The reason, according to Dr. Prendergast, is concern that younger patients might outlive the expected lifespan of the prosthetic TAVI device.
No single criterion for selecting SAVR over TAVI
However, there are many exceptions and additional considerations beyond age. When both SAVR and TAVI are otherwise suitable options, but TAVI cannot be performed with a transfemoral access, Dr. Prendergast pointed out that SAVR might be a better choice.
Transfemoral access is the preferred strategy in TAVI, but Dr. Prendergast emphasized that a collaborative “heart team” should help patients select the most appropriate option. In fact, there is a grade IIb recommendation (“usefulness or efficacy is less well established”) to consider other access sites in patients at high surgical risk with contraindications for transfemoral TAVI.
Of new recommendations in the area of severe aortic stenosis, valvular repair may now be considered in asymptomatic patients with a left ventricular ejection fraction of less than 55%, according to a grade IIb recommendation. The 2017 guidelines did not address this issue.
Grade I recommendation for bioprostheses
A substantial number of the revisions involve minor clarifications without a change in the grade, but a revision regarding bioprosthetics is substantial. In the 2017 guidelines, there was a grade IIa recommendation (“weight of evidence is in favor”) to consider bioprosthetics in patients with a life expectancy less than the expected durability of the device. The 2021 guidelines have changed this to a grade I indication, adding an indication for bioprostheses in patients contraindicated for or unlikely to achieve good-quality anticoagulation.
On this same topic, there is a new grade IIb recommendation to consider bioprosthesis over alternative devices in patients already on a long-term non–vitamin K oral anticoagulant because of the high risk of thromboembolism.
There are two new recommendations in the realm of severe secondary mitral regurgitation, reported Fabien Praz, MD, an interventional cardiologist at the University of Bern (Switzerland). The first, which is perhaps the most significant, is a grade I recommendation for valve surgery in patients with severe secondary mitral regurgitation who remain symptomatic despite optimized medical therapy.
The second is a grade IIa recommendation for invasive procedures, such as a percutaneous coronary intervention, for patients with symptomatic secondary mitral regurgitation and coexisting coronary artery disease. In both cases, however, Dr. Praz emphasized language in the guidelines that calls for a collaborative heart team to agree on the suitability of these treatments.
Ultimately, none of these recommendations can be divorced from patient expectations and values, according to Friedhelm Beyersdorf, MD, chairman of the department of cardiovascular surgery at the Heart Center of the University of Freiburg (Germany).
Even if treatment is not expected to prolong life, “symptom relief on its own may justify intervention,” said Dr. Beyersdorf. However, he emphasized that “thoroughly informed” patients are an essential part of the process in selecting a treatment strategy most likely to satisfy patient goals.
Dr. Vahanian and Dr. Prendergast reported no conflicts of interest relevant to these guidelines. Dr. Praz reported a financial relationship with Edwards Lifesciences. Dr. Beyersdorf reported a financial relationship with Resuscitec.
FROM ESC 2021
Although inconclusive, CV safety study of cancer therapy attracts attention
The first global trial to compare the cardiovascular (CV) safety of two therapies for prostate cancer proved inconclusive because of inadequate enrollment and events, but the study is a harbinger of growth in the emerging specialty of cardio-oncology, according to experts.
“Many new cancer agents have extended patient survival, yet some of these agents have significant potential cardiovascular toxicity,” said Renato D. Lopes, MD, in presenting a study at the annual congress of the European Society of Cardiology.
In the context of improving survival in patients with or at risk for both cancer and cardiovascular disease, he suggested that the prostate cancer study he led could be “a model for interdisciplinary collaboration” needed to address the relative and sometimes competing risks of these disease states.
This point was seconded by several pioneers in cardio-oncology who participated in the discussion of the results of the trial, called PRONOUNCE.
“We know many drugs in oncology increase cardiovascular risk, so these are the types of trials we need,” according Thomas M. Suter, MD, who leads the cardio-oncology service at the University Hospital, Berne, Switzerland. He was the ESC-invited discussant for PRONOUNCE.
More than 100 centers in 12 countries involved
In PRONOUNCE, 545 patients with prostate cancer and established atherosclerotic cardiovascular disease were randomized to degarelix, a gonadotropin-releasing hormone antagonist, or leuprolide, a GnRH agonist. The patients were enrolled at 113 participating centers in 12 countries. All of the patients had an indication for an androgen-deprivation therapy (ADT).
In numerous previous studies, “ADT has been associated with higher CV morbidity and mortality, particularly in men with preexisting CV disease,” explained Dr. Lopes, but the relative cardiovascular safety of GnRH agonists relative to GnRH antagonists has been “controversial.”
The PRONOUNCE study was designed to resolve this issue, but the study was terminated early because of slow enrollment (not related to the COVID-19 pandemic). The planned enrollment was 900 patients.
In addition, the rate of major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or death, was lower over the course of follow-up than anticipated in the study design.
No significant difference on primary endpoint
At the end of 12 months, MACE occurred in 11 (4.1%) of patients randomized to leuprolide and 15 (5.5%) of those randomized to degarelix. The greater hazard ratio for MACE in the degarelix group did not approach statistical significance (hazard ratio, 1.28; P = .53).
As a result, the question of the relative CV safety of these drugs “remains unresolved,” according to Dr. Lopes, professor of medicine at Duke University Medical Center, Durham, N.C.
This does not diminish the need to answer this question. In the addition to the fact that cancer is a malignancy primarily of advancing age when CV disease is prevalent – the mean age in this study was 73 years and 44% were over age 75 – it is often an indolent disease with long periods of survival, according to Dr. Lopes. About half of prostate cancer patients have concomitant CV disease, and about half will receive ADT at some point in their treatment.
In patients receiving ADT, leuprolide is far more commonly used than GnRH antagonists, which are offered in only about 4% of patients, according to data cited by Dr. Lopes. The underlying hypothesis of this study was that leuprolide is associated with greater CV risk, which might have been relevant to a risk-benefit calculation, if the hypothesis had been confirmed.
Cancer drugs can increase CV risk
Based on experimental data, “there is concern the leuprolide is involved in plaque destabilization,” said Dr. Lopes, but he noted that ADTs in general are associated with adverse metabolic changes, including increases in LDL cholesterol, insulin resistance, and body fat, all of which could be relevant to CV risk.
It is the improving rates of survival for prostate cancer as well for other types of cancer that have increased attention to the potential for cancer drugs to increase CV risk, another major cause of early mortality. For these competing risks, objective data are needed to evaluate a relative risk-to-benefit ratio for treatment choices.
This dilemma led the ESC to recently establish its Council on Cardio-Oncology, and many centers around the world are also creating interdisciplinary groups to guide treatment choices for patients with both diseases.
“You will certainly get a lot of referrals,” said Rudolf de Boer, MD, professor of translational cardiology, University Medical Center, Groningen, Netherlands. Basing his remark on his own experience starting a cardio-oncology clinic at his institution, he called this work challenging and agreed that the need for objective data is urgent.
“We need data to provide common ground on which to judge relative risks,” Dr. de Boer said. He also praised the PRONOUNCE investigators for their efforts even if the data failed to answer the question posed.
The PRONOUNCE results were published online in Circulation at the time of Dr. Lopes’s presentation.
The study received funding from Ferring Pharmaceuticals. Dr. Lopes reports financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi. Dr. Suter reports financial relationships with Boehringer Ingelheim, GlaxoSmithKline, and Roche. Dr. de Boer reports financial relationships with AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche.
The first global trial to compare the cardiovascular (CV) safety of two therapies for prostate cancer proved inconclusive because of inadequate enrollment and events, but the study is a harbinger of growth in the emerging specialty of cardio-oncology, according to experts.
“Many new cancer agents have extended patient survival, yet some of these agents have significant potential cardiovascular toxicity,” said Renato D. Lopes, MD, in presenting a study at the annual congress of the European Society of Cardiology.
In the context of improving survival in patients with or at risk for both cancer and cardiovascular disease, he suggested that the prostate cancer study he led could be “a model for interdisciplinary collaboration” needed to address the relative and sometimes competing risks of these disease states.
This point was seconded by several pioneers in cardio-oncology who participated in the discussion of the results of the trial, called PRONOUNCE.
“We know many drugs in oncology increase cardiovascular risk, so these are the types of trials we need,” according Thomas M. Suter, MD, who leads the cardio-oncology service at the University Hospital, Berne, Switzerland. He was the ESC-invited discussant for PRONOUNCE.
More than 100 centers in 12 countries involved
In PRONOUNCE, 545 patients with prostate cancer and established atherosclerotic cardiovascular disease were randomized to degarelix, a gonadotropin-releasing hormone antagonist, or leuprolide, a GnRH agonist. The patients were enrolled at 113 participating centers in 12 countries. All of the patients had an indication for an androgen-deprivation therapy (ADT).
In numerous previous studies, “ADT has been associated with higher CV morbidity and mortality, particularly in men with preexisting CV disease,” explained Dr. Lopes, but the relative cardiovascular safety of GnRH agonists relative to GnRH antagonists has been “controversial.”
The PRONOUNCE study was designed to resolve this issue, but the study was terminated early because of slow enrollment (not related to the COVID-19 pandemic). The planned enrollment was 900 patients.
In addition, the rate of major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or death, was lower over the course of follow-up than anticipated in the study design.
No significant difference on primary endpoint
At the end of 12 months, MACE occurred in 11 (4.1%) of patients randomized to leuprolide and 15 (5.5%) of those randomized to degarelix. The greater hazard ratio for MACE in the degarelix group did not approach statistical significance (hazard ratio, 1.28; P = .53).
As a result, the question of the relative CV safety of these drugs “remains unresolved,” according to Dr. Lopes, professor of medicine at Duke University Medical Center, Durham, N.C.
This does not diminish the need to answer this question. In the addition to the fact that cancer is a malignancy primarily of advancing age when CV disease is prevalent – the mean age in this study was 73 years and 44% were over age 75 – it is often an indolent disease with long periods of survival, according to Dr. Lopes. About half of prostate cancer patients have concomitant CV disease, and about half will receive ADT at some point in their treatment.
In patients receiving ADT, leuprolide is far more commonly used than GnRH antagonists, which are offered in only about 4% of patients, according to data cited by Dr. Lopes. The underlying hypothesis of this study was that leuprolide is associated with greater CV risk, which might have been relevant to a risk-benefit calculation, if the hypothesis had been confirmed.
Cancer drugs can increase CV risk
Based on experimental data, “there is concern the leuprolide is involved in plaque destabilization,” said Dr. Lopes, but he noted that ADTs in general are associated with adverse metabolic changes, including increases in LDL cholesterol, insulin resistance, and body fat, all of which could be relevant to CV risk.
It is the improving rates of survival for prostate cancer as well for other types of cancer that have increased attention to the potential for cancer drugs to increase CV risk, another major cause of early mortality. For these competing risks, objective data are needed to evaluate a relative risk-to-benefit ratio for treatment choices.
This dilemma led the ESC to recently establish its Council on Cardio-Oncology, and many centers around the world are also creating interdisciplinary groups to guide treatment choices for patients with both diseases.
“You will certainly get a lot of referrals,” said Rudolf de Boer, MD, professor of translational cardiology, University Medical Center, Groningen, Netherlands. Basing his remark on his own experience starting a cardio-oncology clinic at his institution, he called this work challenging and agreed that the need for objective data is urgent.
“We need data to provide common ground on which to judge relative risks,” Dr. de Boer said. He also praised the PRONOUNCE investigators for their efforts even if the data failed to answer the question posed.
The PRONOUNCE results were published online in Circulation at the time of Dr. Lopes’s presentation.
The study received funding from Ferring Pharmaceuticals. Dr. Lopes reports financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi. Dr. Suter reports financial relationships with Boehringer Ingelheim, GlaxoSmithKline, and Roche. Dr. de Boer reports financial relationships with AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche.
The first global trial to compare the cardiovascular (CV) safety of two therapies for prostate cancer proved inconclusive because of inadequate enrollment and events, but the study is a harbinger of growth in the emerging specialty of cardio-oncology, according to experts.
“Many new cancer agents have extended patient survival, yet some of these agents have significant potential cardiovascular toxicity,” said Renato D. Lopes, MD, in presenting a study at the annual congress of the European Society of Cardiology.
In the context of improving survival in patients with or at risk for both cancer and cardiovascular disease, he suggested that the prostate cancer study he led could be “a model for interdisciplinary collaboration” needed to address the relative and sometimes competing risks of these disease states.
This point was seconded by several pioneers in cardio-oncology who participated in the discussion of the results of the trial, called PRONOUNCE.
“We know many drugs in oncology increase cardiovascular risk, so these are the types of trials we need,” according Thomas M. Suter, MD, who leads the cardio-oncology service at the University Hospital, Berne, Switzerland. He was the ESC-invited discussant for PRONOUNCE.
More than 100 centers in 12 countries involved
In PRONOUNCE, 545 patients with prostate cancer and established atherosclerotic cardiovascular disease were randomized to degarelix, a gonadotropin-releasing hormone antagonist, or leuprolide, a GnRH agonist. The patients were enrolled at 113 participating centers in 12 countries. All of the patients had an indication for an androgen-deprivation therapy (ADT).
In numerous previous studies, “ADT has been associated with higher CV morbidity and mortality, particularly in men with preexisting CV disease,” explained Dr. Lopes, but the relative cardiovascular safety of GnRH agonists relative to GnRH antagonists has been “controversial.”
The PRONOUNCE study was designed to resolve this issue, but the study was terminated early because of slow enrollment (not related to the COVID-19 pandemic). The planned enrollment was 900 patients.
In addition, the rate of major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or death, was lower over the course of follow-up than anticipated in the study design.
No significant difference on primary endpoint
At the end of 12 months, MACE occurred in 11 (4.1%) of patients randomized to leuprolide and 15 (5.5%) of those randomized to degarelix. The greater hazard ratio for MACE in the degarelix group did not approach statistical significance (hazard ratio, 1.28; P = .53).
As a result, the question of the relative CV safety of these drugs “remains unresolved,” according to Dr. Lopes, professor of medicine at Duke University Medical Center, Durham, N.C.
This does not diminish the need to answer this question. In the addition to the fact that cancer is a malignancy primarily of advancing age when CV disease is prevalent – the mean age in this study was 73 years and 44% were over age 75 – it is often an indolent disease with long periods of survival, according to Dr. Lopes. About half of prostate cancer patients have concomitant CV disease, and about half will receive ADT at some point in their treatment.
In patients receiving ADT, leuprolide is far more commonly used than GnRH antagonists, which are offered in only about 4% of patients, according to data cited by Dr. Lopes. The underlying hypothesis of this study was that leuprolide is associated with greater CV risk, which might have been relevant to a risk-benefit calculation, if the hypothesis had been confirmed.
Cancer drugs can increase CV risk
Based on experimental data, “there is concern the leuprolide is involved in plaque destabilization,” said Dr. Lopes, but he noted that ADTs in general are associated with adverse metabolic changes, including increases in LDL cholesterol, insulin resistance, and body fat, all of which could be relevant to CV risk.
It is the improving rates of survival for prostate cancer as well for other types of cancer that have increased attention to the potential for cancer drugs to increase CV risk, another major cause of early mortality. For these competing risks, objective data are needed to evaluate a relative risk-to-benefit ratio for treatment choices.
This dilemma led the ESC to recently establish its Council on Cardio-Oncology, and many centers around the world are also creating interdisciplinary groups to guide treatment choices for patients with both diseases.
“You will certainly get a lot of referrals,” said Rudolf de Boer, MD, professor of translational cardiology, University Medical Center, Groningen, Netherlands. Basing his remark on his own experience starting a cardio-oncology clinic at his institution, he called this work challenging and agreed that the need for objective data is urgent.
“We need data to provide common ground on which to judge relative risks,” Dr. de Boer said. He also praised the PRONOUNCE investigators for their efforts even if the data failed to answer the question posed.
The PRONOUNCE results were published online in Circulation at the time of Dr. Lopes’s presentation.
The study received funding from Ferring Pharmaceuticals. Dr. Lopes reports financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi. Dr. Suter reports financial relationships with Boehringer Ingelheim, GlaxoSmithKline, and Roche. Dr. de Boer reports financial relationships with AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche.
FROM ESC 2021
In all-comer approach, FFR adds no value to angiography: RIPCORD 2
Study confirms selective application
In patients with coronary artery disease scheduled for a percutaneous intervention (PCI), fractional flow reserve (FFR) assessment at the time of angiography significantly improves outcome, but it has no apparent value as a routine study in all CAD patients, according to the randomized RIPCORD 2 trial.
When compared to angiography alone in an all comer-strategy, the addition of FFR did not significantly change management or lower costs, but it was associated with a longer time for diagnostic assessment and more complications, Nicholas P. Curzen, BM, PhD, reported at the annual congress of the European Society of Cardiology.
As a tool for evaluating stenotic lesions in diseased vessels, FFR, also known as pressure wire assessment, allows interventionalists to target those vessels that induce ischemia without unnecessarily treating vessels with lesions that are hemodynamically nonsignificant. It is guideline recommended for patients with scheduled PCI on the basis of several randomized trials, including the landmark FAME trial.
“The results of these trials were spectacular. The clinical outcomes were significantly better in the FFR group despite less stents being placed and fewer vessels being stented. And there was significantly less resource utilization in the FFR group,” said Dr. Curzen, professor of interventional cardiology, University of Southampton, England.
Hypothesis: All-comers benefit from FFR
This prompted the new trial, called RIPCORD 2. The hypothesis was that systematic FFR early in the diagnosis of CAD would reduce resource utilization and improve quality of life relative to angiography alone. Both were addressed as primary endpoints. A reduction in clinical events at 12 months was a secondary endpoint.
The 1,136 participants, all scheduled for angiographic evaluation for stable angina or non-ST elevated myocardial infarction (NSTEMI), were randomized at 17 participating centers in the United Kingdom. All underwent angiography, but the experimental arm also underwent FFR for all arteries of a size suitable for revascularization.
Resource utilization evaluated through hospital costs at 12 months was somewhat higher in the FFR group, but the difference was not significant (P =.137). There was also no significant difference (P = 0.88) between the groups in quality of life, which was measured with EQ-5D-5L, an instrument for expressing five dimensions of health on a visual analog scale.
No impact from FFR on clinical events
Furthermore, there was no difference in the rate of clinical events, whether measured by a composite endpoint of major adverse cardiac events (MACE) (P = .64) or by the components of death, stroke, myocardial infarction, and unplanned revascularization, according to Dr. Curzen.
Finally, FFR did not appear to influence subsequent management. When the intervention and control groups were compared, the proportions triaged to optimal medical therapy, optimal medical therapy plus PCI, or optimal medical therapy plus bypass grafting did not differ significantly.
Given the lack of significant differences for FFR plus angiography relative to angiography alone for any clinically relevant outcome, the addition of FFR provides "no overall advantage" in this all comer study population, Dr. Curzen concluded.
However, FFR was associated with some relative disadvantages. These included significantly longer mean procedure times (69 vs. 42.4 minutes; P < .001), significantly greater mean use of contrast (206 vs. 146.3 mL; P < .001), and a significantly higher mean radiation dose (6608.7 vs. 5029.7 cGY/cm2; P < .001). There were 10 complications (1.8%) associated with FFR.
RIPCORD 1 results provided study rationale
In the previously published nonrandomized RIPCORD 1 study, interventionalists were asked to develop a management plan on the basis of angiography alone in 200 patients with stable chest pain. When these interventionalists were then provided with FFR results, the new information resulted in a change of management plan in 36% of cases.
According to Dr. Curzen, it was this study that raised all-comer FFR as a “logical and clinically plausible question.” RIPCORD 2 provided the answer.
While he is now conducting an evaluation of a subgroup of RIPCORD 2 patients with more severe disease, “it appears that the atheroma burden on angiography is adequate” to make an appropriate management determination in most or all cases.
The invited discussant for this study, Robert Byrne, MD, BCh, PhD, director of cardiology, Mater Private Hospital, Dublin, pointed out that more angiography-alone patients in RIPCORD 2 required additional evaluation to develop a management strategy (14.7% vs. 1.8%), but he agreed that FFR offered “no reasonable benefit” in the relatively low-risk patients who were enrolled.
Results do not alter FFR indications
However, he emphasized that the lack of an advantage in this trial should in no way diminish the evidence of benefit for selective FFR use as currently recommended in guidelines. This was echoed strongly in remarks by two other interventionalists who served on the same panel after the RIPCORD 2 results were presented.
“I want to make sure that our audience does not walk away thinking that FFR is useless. This is not what was shown,” said Roxana Mehran, MD, director of interventional cardiovascular research at Icahn School of Medicine at Mount Sinai, New York. She emphasized that this was a study that found no value in a low-risk, all-comer population and is not relevant to the populations where it now has an indication.
Marco Roffi, MD, director of the interventional cardiology unit, Geneva University Hospitals, made the same point.
“These results do not take away the value of FFR in a more selected population [than that enrolled in RIPCORD 2],” Dr. Roffi said. He did not rule out the potential for benefit from adding FFR to angiography even in early disease assessment if a benefit can be demonstrated in a higher-risk population.
Dr. Curzen reports financial relationships with Abbott, Beckman Coulter, HeartFlow, and Boston Scientific, which provided funding for RIPCORD 2. Dr. Byrne reported financial relationships with the trial sponsor as well as Abbott, Biosensors, and Biotronik. Dr. Mehran reports financial relationships with more than 15 medical product companies including the sponsor of this trial. Dr. Roffi reports no relevant financial disclosures.
Study confirms selective application
Study confirms selective application
In patients with coronary artery disease scheduled for a percutaneous intervention (PCI), fractional flow reserve (FFR) assessment at the time of angiography significantly improves outcome, but it has no apparent value as a routine study in all CAD patients, according to the randomized RIPCORD 2 trial.
When compared to angiography alone in an all comer-strategy, the addition of FFR did not significantly change management or lower costs, but it was associated with a longer time for diagnostic assessment and more complications, Nicholas P. Curzen, BM, PhD, reported at the annual congress of the European Society of Cardiology.
As a tool for evaluating stenotic lesions in diseased vessels, FFR, also known as pressure wire assessment, allows interventionalists to target those vessels that induce ischemia without unnecessarily treating vessels with lesions that are hemodynamically nonsignificant. It is guideline recommended for patients with scheduled PCI on the basis of several randomized trials, including the landmark FAME trial.
“The results of these trials were spectacular. The clinical outcomes were significantly better in the FFR group despite less stents being placed and fewer vessels being stented. And there was significantly less resource utilization in the FFR group,” said Dr. Curzen, professor of interventional cardiology, University of Southampton, England.
Hypothesis: All-comers benefit from FFR
This prompted the new trial, called RIPCORD 2. The hypothesis was that systematic FFR early in the diagnosis of CAD would reduce resource utilization and improve quality of life relative to angiography alone. Both were addressed as primary endpoints. A reduction in clinical events at 12 months was a secondary endpoint.
The 1,136 participants, all scheduled for angiographic evaluation for stable angina or non-ST elevated myocardial infarction (NSTEMI), were randomized at 17 participating centers in the United Kingdom. All underwent angiography, but the experimental arm also underwent FFR for all arteries of a size suitable for revascularization.
Resource utilization evaluated through hospital costs at 12 months was somewhat higher in the FFR group, but the difference was not significant (P =.137). There was also no significant difference (P = 0.88) between the groups in quality of life, which was measured with EQ-5D-5L, an instrument for expressing five dimensions of health on a visual analog scale.
No impact from FFR on clinical events
Furthermore, there was no difference in the rate of clinical events, whether measured by a composite endpoint of major adverse cardiac events (MACE) (P = .64) or by the components of death, stroke, myocardial infarction, and unplanned revascularization, according to Dr. Curzen.
Finally, FFR did not appear to influence subsequent management. When the intervention and control groups were compared, the proportions triaged to optimal medical therapy, optimal medical therapy plus PCI, or optimal medical therapy plus bypass grafting did not differ significantly.
Given the lack of significant differences for FFR plus angiography relative to angiography alone for any clinically relevant outcome, the addition of FFR provides "no overall advantage" in this all comer study population, Dr. Curzen concluded.
However, FFR was associated with some relative disadvantages. These included significantly longer mean procedure times (69 vs. 42.4 minutes; P < .001), significantly greater mean use of contrast (206 vs. 146.3 mL; P < .001), and a significantly higher mean radiation dose (6608.7 vs. 5029.7 cGY/cm2; P < .001). There were 10 complications (1.8%) associated with FFR.
RIPCORD 1 results provided study rationale
In the previously published nonrandomized RIPCORD 1 study, interventionalists were asked to develop a management plan on the basis of angiography alone in 200 patients with stable chest pain. When these interventionalists were then provided with FFR results, the new information resulted in a change of management plan in 36% of cases.
According to Dr. Curzen, it was this study that raised all-comer FFR as a “logical and clinically plausible question.” RIPCORD 2 provided the answer.
While he is now conducting an evaluation of a subgroup of RIPCORD 2 patients with more severe disease, “it appears that the atheroma burden on angiography is adequate” to make an appropriate management determination in most or all cases.
The invited discussant for this study, Robert Byrne, MD, BCh, PhD, director of cardiology, Mater Private Hospital, Dublin, pointed out that more angiography-alone patients in RIPCORD 2 required additional evaluation to develop a management strategy (14.7% vs. 1.8%), but he agreed that FFR offered “no reasonable benefit” in the relatively low-risk patients who were enrolled.
Results do not alter FFR indications
However, he emphasized that the lack of an advantage in this trial should in no way diminish the evidence of benefit for selective FFR use as currently recommended in guidelines. This was echoed strongly in remarks by two other interventionalists who served on the same panel after the RIPCORD 2 results were presented.
“I want to make sure that our audience does not walk away thinking that FFR is useless. This is not what was shown,” said Roxana Mehran, MD, director of interventional cardiovascular research at Icahn School of Medicine at Mount Sinai, New York. She emphasized that this was a study that found no value in a low-risk, all-comer population and is not relevant to the populations where it now has an indication.
Marco Roffi, MD, director of the interventional cardiology unit, Geneva University Hospitals, made the same point.
“These results do not take away the value of FFR in a more selected population [than that enrolled in RIPCORD 2],” Dr. Roffi said. He did not rule out the potential for benefit from adding FFR to angiography even in early disease assessment if a benefit can be demonstrated in a higher-risk population.
Dr. Curzen reports financial relationships with Abbott, Beckman Coulter, HeartFlow, and Boston Scientific, which provided funding for RIPCORD 2. Dr. Byrne reported financial relationships with the trial sponsor as well as Abbott, Biosensors, and Biotronik. Dr. Mehran reports financial relationships with more than 15 medical product companies including the sponsor of this trial. Dr. Roffi reports no relevant financial disclosures.
In patients with coronary artery disease scheduled for a percutaneous intervention (PCI), fractional flow reserve (FFR) assessment at the time of angiography significantly improves outcome, but it has no apparent value as a routine study in all CAD patients, according to the randomized RIPCORD 2 trial.
When compared to angiography alone in an all comer-strategy, the addition of FFR did not significantly change management or lower costs, but it was associated with a longer time for diagnostic assessment and more complications, Nicholas P. Curzen, BM, PhD, reported at the annual congress of the European Society of Cardiology.
As a tool for evaluating stenotic lesions in diseased vessels, FFR, also known as pressure wire assessment, allows interventionalists to target those vessels that induce ischemia without unnecessarily treating vessels with lesions that are hemodynamically nonsignificant. It is guideline recommended for patients with scheduled PCI on the basis of several randomized trials, including the landmark FAME trial.
“The results of these trials were spectacular. The clinical outcomes were significantly better in the FFR group despite less stents being placed and fewer vessels being stented. And there was significantly less resource utilization in the FFR group,” said Dr. Curzen, professor of interventional cardiology, University of Southampton, England.
Hypothesis: All-comers benefit from FFR
This prompted the new trial, called RIPCORD 2. The hypothesis was that systematic FFR early in the diagnosis of CAD would reduce resource utilization and improve quality of life relative to angiography alone. Both were addressed as primary endpoints. A reduction in clinical events at 12 months was a secondary endpoint.
The 1,136 participants, all scheduled for angiographic evaluation for stable angina or non-ST elevated myocardial infarction (NSTEMI), were randomized at 17 participating centers in the United Kingdom. All underwent angiography, but the experimental arm also underwent FFR for all arteries of a size suitable for revascularization.
Resource utilization evaluated through hospital costs at 12 months was somewhat higher in the FFR group, but the difference was not significant (P =.137). There was also no significant difference (P = 0.88) between the groups in quality of life, which was measured with EQ-5D-5L, an instrument for expressing five dimensions of health on a visual analog scale.
No impact from FFR on clinical events
Furthermore, there was no difference in the rate of clinical events, whether measured by a composite endpoint of major adverse cardiac events (MACE) (P = .64) or by the components of death, stroke, myocardial infarction, and unplanned revascularization, according to Dr. Curzen.
Finally, FFR did not appear to influence subsequent management. When the intervention and control groups were compared, the proportions triaged to optimal medical therapy, optimal medical therapy plus PCI, or optimal medical therapy plus bypass grafting did not differ significantly.
Given the lack of significant differences for FFR plus angiography relative to angiography alone for any clinically relevant outcome, the addition of FFR provides "no overall advantage" in this all comer study population, Dr. Curzen concluded.
However, FFR was associated with some relative disadvantages. These included significantly longer mean procedure times (69 vs. 42.4 minutes; P < .001), significantly greater mean use of contrast (206 vs. 146.3 mL; P < .001), and a significantly higher mean radiation dose (6608.7 vs. 5029.7 cGY/cm2; P < .001). There were 10 complications (1.8%) associated with FFR.
RIPCORD 1 results provided study rationale
In the previously published nonrandomized RIPCORD 1 study, interventionalists were asked to develop a management plan on the basis of angiography alone in 200 patients with stable chest pain. When these interventionalists were then provided with FFR results, the new information resulted in a change of management plan in 36% of cases.
According to Dr. Curzen, it was this study that raised all-comer FFR as a “logical and clinically plausible question.” RIPCORD 2 provided the answer.
While he is now conducting an evaluation of a subgroup of RIPCORD 2 patients with more severe disease, “it appears that the atheroma burden on angiography is adequate” to make an appropriate management determination in most or all cases.
The invited discussant for this study, Robert Byrne, MD, BCh, PhD, director of cardiology, Mater Private Hospital, Dublin, pointed out that more angiography-alone patients in RIPCORD 2 required additional evaluation to develop a management strategy (14.7% vs. 1.8%), but he agreed that FFR offered “no reasonable benefit” in the relatively low-risk patients who were enrolled.
Results do not alter FFR indications
However, he emphasized that the lack of an advantage in this trial should in no way diminish the evidence of benefit for selective FFR use as currently recommended in guidelines. This was echoed strongly in remarks by two other interventionalists who served on the same panel after the RIPCORD 2 results were presented.
“I want to make sure that our audience does not walk away thinking that FFR is useless. This is not what was shown,” said Roxana Mehran, MD, director of interventional cardiovascular research at Icahn School of Medicine at Mount Sinai, New York. She emphasized that this was a study that found no value in a low-risk, all-comer population and is not relevant to the populations where it now has an indication.
Marco Roffi, MD, director of the interventional cardiology unit, Geneva University Hospitals, made the same point.
“These results do not take away the value of FFR in a more selected population [than that enrolled in RIPCORD 2],” Dr. Roffi said. He did not rule out the potential for benefit from adding FFR to angiography even in early disease assessment if a benefit can be demonstrated in a higher-risk population.
Dr. Curzen reports financial relationships with Abbott, Beckman Coulter, HeartFlow, and Boston Scientific, which provided funding for RIPCORD 2. Dr. Byrne reported financial relationships with the trial sponsor as well as Abbott, Biosensors, and Biotronik. Dr. Mehran reports financial relationships with more than 15 medical product companies including the sponsor of this trial. Dr. Roffi reports no relevant financial disclosures.
FROM ESC CONGRESS 2021
Ablation at an early stage of fibrosis appears critical to improved AFib control
No benefit observed if fibrosis advanced
The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.
However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.
“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.
The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.
After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
Five percent risk reduction not significant
After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).
As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.
In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.
“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.
Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).
Subgroup data called clinically meaningful
“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”
Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.
“If the fibrosis is advanced, do PVI only,” he said.
However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.
“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”
Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
DECAAF II is not a positive trial
Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.
In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”
Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.
An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”
He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.
“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.
Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.
No benefit observed if fibrosis advanced
No benefit observed if fibrosis advanced
The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.
However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.
“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.
The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.
After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
Five percent risk reduction not significant
After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).
As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.
In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.
“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.
Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).
Subgroup data called clinically meaningful
“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”
Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.
“If the fibrosis is advanced, do PVI only,” he said.
However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.
“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”
Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
DECAAF II is not a positive trial
Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.
In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”
Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.
An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”
He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.
“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.
Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.
The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.
However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.
“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.
The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.
After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
Five percent risk reduction not significant
After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).
As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.
In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.
“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.
Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).
Subgroup data called clinically meaningful
“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”
Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.
“If the fibrosis is advanced, do PVI only,” he said.
However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.
“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”
Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
DECAAF II is not a positive trial
Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.
In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”
Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.
An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”
He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.
“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.
Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.
FROM ESC CONGRESS 2021
ICMs detect serious arrhythmias in high-risk post-MI patients: SMART-MI
Prevention strategies may be next
After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.
When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.
The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).
“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”
The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.
Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.
The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
ECG used to define autonomic dysfunction
In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.
The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.
After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.
The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).
Arrhythmias warn of impending complications
“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”
Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.
“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”
Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.
“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
Data provide insight on unaddressed risk group
SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.
An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.
“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.
Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.
Prevention strategies may be next
Prevention strategies may be next
After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.
When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.
The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).
“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”
The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.
Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.
The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
ECG used to define autonomic dysfunction
In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.
The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.
After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.
The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).
Arrhythmias warn of impending complications
“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”
Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.
“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”
Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.
“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
Data provide insight on unaddressed risk group
SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.
An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.
“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.
Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.
After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.
When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.
The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).
“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”
The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.
Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.
The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
ECG used to define autonomic dysfunction
In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.
The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.
After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.
The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).
Arrhythmias warn of impending complications
“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”
Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.
“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”
Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.
“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
Data provide insight on unaddressed risk group
SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.
An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.
“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.
Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.
FROM ESC CONGRESS 2021