User login
Atrial fibrosis weighed as key arrhythmia, stroke trigger
ORLANDO – , particularly strokes, and has also become the target for ablative strategies by some operators for more effective rhythm control in patients with atrial fibrillation.
“A strong and graded association exists between the severity of left atrial fibrosis severity and major cardiovascular adverse events, primarily due to stroke, transient ischemic attack, and heart failure, Nassir F. Marrouche, MD, said at the annual International AF Symposium.
Atrial fibrosis is quantified noninvasively by Dr. Marrouche and his associates with late gadolinium enhancement MRI. They published results of a retrospective study in 2017 showing that, during follow-up of 1,228 patients from their center with atrial fibrillation, the 5% of patients who had the highest level of left atrial fibrosis – 30% or more of left atrial tissue – had a significantly increased rate of cardiovascular events during follow-up, compared with the 35% of studied patients with fibrosis constituting less than 10% of their left atrium. The remaining 60% of studied patients had fibrotic tissue that formed 10%-29% of their total left atrial area.
This relationship was strongest when the analysis focused exclusively on the incidence of strokes or transient ischemic attacks. These events occurred nearly fourfold more often among patients with the highest amount of fibrosis, compared with those with the least (J Amer Coll Cardiol. 2017 Sep;70[11]:311-21).
Given that the finding came from a retrospective, single-center study, the clinical implication of fibrosis remains too uncertain to apply to current routine practice. But Dr. Marrouche strongly suspects that fibrotic tissue in the left atrium serves as a potent trigger of thrombosis.
“We think that even patients with a CHA2DS2-VASc score of zero who have a high level of fibrosis may need treatment with an anticoagulant, but we need a prospective study” to validate this, Dr. Marrouche said.
Another area for further research is to explore agents that may be able to prevent or reverse fibrosis in the left atrium. One candidate class of drugs are the angiotensin-converting enzyme inhibitors, he said in an interview.
Atrial fibrosis can have a variety of causes, including hypertension, inflammation, genetics, frequent high-intensity exercise, or other histories that produce regular intervals of extreme atrial stretch, he noted.
Dr. Marrouche is leading a multicenter trial that will test the efficacy of an ablation method for patients with atrial fibrillation tailored to isolating heavily fibrotic regions of the atria. The Efficacy of Delayed Enhancement MRI-Guided Ablation vs. Conventional Catheter Ablation of Atrial Fibrillation (DECAAFII) trial is comparing ablation aimed at fibrotic regions against conventional ablation in about 900 patients. Results are expected in another 2-3 years.
Although the usefulness of ablation aimed at isolating areas of fibrosis in the atrium remains unproven, this approach has already been embraced by some operators, including Hans Kottkamp, MD, a professor and electrophysiologist at Hirslanden Hospital in Zurich.
“Fibrosis is the fundamental histologic finding and the key pathophysiologic player in atrial fibrillation,” Dr. Kottkamp said in a separate talk at the meeting. “We suggest doing ablation based on the substrate, and not based on whether the atrial fibrillation is paroxysmal or persistent.” His group uses voltage mapping instead of MRI as their tool for quantifying the amount of fibrosis and pinpointing its location.
“The fibrosis is usually regionalized; it’s not everywhere” in the left atrium, Dr. Kottkamp noted, and the location is very individualized. “You need to look for it in each patient.”
In his experience, about 20% of patients with paroxysmal AF have enough atrial fibrosis to warrant using BIFA along with pulmonary vein isolation. “Among patients with persistent AF, the percentage with significant fibrosis rises to about two-thirds,” Dr. Kottkamp said in an interview. Combining BIFA with pulmonary vein isolation in these patients with higher fibrosis substantially boosts procedural success.
In a recent report, Dr. Kottkamp and his associates presented their experience using BIFA on 92 patients with AF and fibrotic atrial cardiomyopathy. The outcomes showed a relatively high level of success in resolving the AF after an average follow-up of 16 months, with a 69% success rate after a single procedure and an 83% success rate when selected patients received a second BIFA.
Overall, each patient in the series received an average of 1.2 BIFA ablations (J Cardiovasc Electrophysiol. 2017 Sep;28[9]:971-83).
Currently, a limited number of other groups uses BIFA or a similar fibrosis-based ablation approach, and these strategies have not yet undergone prospective assessment in a multicenter study. Despite that, Dr. Kottkamp said he was “confident it will become standard of care.”
Dr. Marrouche has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marreck, Medtronic, Preventice, VytronUS, and Wavelet Health, and he has received research support from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Sciences, and VytronUS. Dr. Kottkamp has been a consultant to Biosense Webster and has been a consultant to and has an equity interest in Kardium.
ORLANDO – , particularly strokes, and has also become the target for ablative strategies by some operators for more effective rhythm control in patients with atrial fibrillation.
“A strong and graded association exists between the severity of left atrial fibrosis severity and major cardiovascular adverse events, primarily due to stroke, transient ischemic attack, and heart failure, Nassir F. Marrouche, MD, said at the annual International AF Symposium.
Atrial fibrosis is quantified noninvasively by Dr. Marrouche and his associates with late gadolinium enhancement MRI. They published results of a retrospective study in 2017 showing that, during follow-up of 1,228 patients from their center with atrial fibrillation, the 5% of patients who had the highest level of left atrial fibrosis – 30% or more of left atrial tissue – had a significantly increased rate of cardiovascular events during follow-up, compared with the 35% of studied patients with fibrosis constituting less than 10% of their left atrium. The remaining 60% of studied patients had fibrotic tissue that formed 10%-29% of their total left atrial area.
This relationship was strongest when the analysis focused exclusively on the incidence of strokes or transient ischemic attacks. These events occurred nearly fourfold more often among patients with the highest amount of fibrosis, compared with those with the least (J Amer Coll Cardiol. 2017 Sep;70[11]:311-21).
Given that the finding came from a retrospective, single-center study, the clinical implication of fibrosis remains too uncertain to apply to current routine practice. But Dr. Marrouche strongly suspects that fibrotic tissue in the left atrium serves as a potent trigger of thrombosis.
“We think that even patients with a CHA2DS2-VASc score of zero who have a high level of fibrosis may need treatment with an anticoagulant, but we need a prospective study” to validate this, Dr. Marrouche said.
Another area for further research is to explore agents that may be able to prevent or reverse fibrosis in the left atrium. One candidate class of drugs are the angiotensin-converting enzyme inhibitors, he said in an interview.
Atrial fibrosis can have a variety of causes, including hypertension, inflammation, genetics, frequent high-intensity exercise, or other histories that produce regular intervals of extreme atrial stretch, he noted.
Dr. Marrouche is leading a multicenter trial that will test the efficacy of an ablation method for patients with atrial fibrillation tailored to isolating heavily fibrotic regions of the atria. The Efficacy of Delayed Enhancement MRI-Guided Ablation vs. Conventional Catheter Ablation of Atrial Fibrillation (DECAAFII) trial is comparing ablation aimed at fibrotic regions against conventional ablation in about 900 patients. Results are expected in another 2-3 years.
Although the usefulness of ablation aimed at isolating areas of fibrosis in the atrium remains unproven, this approach has already been embraced by some operators, including Hans Kottkamp, MD, a professor and electrophysiologist at Hirslanden Hospital in Zurich.
“Fibrosis is the fundamental histologic finding and the key pathophysiologic player in atrial fibrillation,” Dr. Kottkamp said in a separate talk at the meeting. “We suggest doing ablation based on the substrate, and not based on whether the atrial fibrillation is paroxysmal or persistent.” His group uses voltage mapping instead of MRI as their tool for quantifying the amount of fibrosis and pinpointing its location.
“The fibrosis is usually regionalized; it’s not everywhere” in the left atrium, Dr. Kottkamp noted, and the location is very individualized. “You need to look for it in each patient.”
In his experience, about 20% of patients with paroxysmal AF have enough atrial fibrosis to warrant using BIFA along with pulmonary vein isolation. “Among patients with persistent AF, the percentage with significant fibrosis rises to about two-thirds,” Dr. Kottkamp said in an interview. Combining BIFA with pulmonary vein isolation in these patients with higher fibrosis substantially boosts procedural success.
In a recent report, Dr. Kottkamp and his associates presented their experience using BIFA on 92 patients with AF and fibrotic atrial cardiomyopathy. The outcomes showed a relatively high level of success in resolving the AF after an average follow-up of 16 months, with a 69% success rate after a single procedure and an 83% success rate when selected patients received a second BIFA.
Overall, each patient in the series received an average of 1.2 BIFA ablations (J Cardiovasc Electrophysiol. 2017 Sep;28[9]:971-83).
Currently, a limited number of other groups uses BIFA or a similar fibrosis-based ablation approach, and these strategies have not yet undergone prospective assessment in a multicenter study. Despite that, Dr. Kottkamp said he was “confident it will become standard of care.”
Dr. Marrouche has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marreck, Medtronic, Preventice, VytronUS, and Wavelet Health, and he has received research support from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Sciences, and VytronUS. Dr. Kottkamp has been a consultant to Biosense Webster and has been a consultant to and has an equity interest in Kardium.
ORLANDO – , particularly strokes, and has also become the target for ablative strategies by some operators for more effective rhythm control in patients with atrial fibrillation.
“A strong and graded association exists between the severity of left atrial fibrosis severity and major cardiovascular adverse events, primarily due to stroke, transient ischemic attack, and heart failure, Nassir F. Marrouche, MD, said at the annual International AF Symposium.
Atrial fibrosis is quantified noninvasively by Dr. Marrouche and his associates with late gadolinium enhancement MRI. They published results of a retrospective study in 2017 showing that, during follow-up of 1,228 patients from their center with atrial fibrillation, the 5% of patients who had the highest level of left atrial fibrosis – 30% or more of left atrial tissue – had a significantly increased rate of cardiovascular events during follow-up, compared with the 35% of studied patients with fibrosis constituting less than 10% of their left atrium. The remaining 60% of studied patients had fibrotic tissue that formed 10%-29% of their total left atrial area.
This relationship was strongest when the analysis focused exclusively on the incidence of strokes or transient ischemic attacks. These events occurred nearly fourfold more often among patients with the highest amount of fibrosis, compared with those with the least (J Amer Coll Cardiol. 2017 Sep;70[11]:311-21).
Given that the finding came from a retrospective, single-center study, the clinical implication of fibrosis remains too uncertain to apply to current routine practice. But Dr. Marrouche strongly suspects that fibrotic tissue in the left atrium serves as a potent trigger of thrombosis.
“We think that even patients with a CHA2DS2-VASc score of zero who have a high level of fibrosis may need treatment with an anticoagulant, but we need a prospective study” to validate this, Dr. Marrouche said.
Another area for further research is to explore agents that may be able to prevent or reverse fibrosis in the left atrium. One candidate class of drugs are the angiotensin-converting enzyme inhibitors, he said in an interview.
Atrial fibrosis can have a variety of causes, including hypertension, inflammation, genetics, frequent high-intensity exercise, or other histories that produce regular intervals of extreme atrial stretch, he noted.
Dr. Marrouche is leading a multicenter trial that will test the efficacy of an ablation method for patients with atrial fibrillation tailored to isolating heavily fibrotic regions of the atria. The Efficacy of Delayed Enhancement MRI-Guided Ablation vs. Conventional Catheter Ablation of Atrial Fibrillation (DECAAFII) trial is comparing ablation aimed at fibrotic regions against conventional ablation in about 900 patients. Results are expected in another 2-3 years.
Although the usefulness of ablation aimed at isolating areas of fibrosis in the atrium remains unproven, this approach has already been embraced by some operators, including Hans Kottkamp, MD, a professor and electrophysiologist at Hirslanden Hospital in Zurich.
“Fibrosis is the fundamental histologic finding and the key pathophysiologic player in atrial fibrillation,” Dr. Kottkamp said in a separate talk at the meeting. “We suggest doing ablation based on the substrate, and not based on whether the atrial fibrillation is paroxysmal or persistent.” His group uses voltage mapping instead of MRI as their tool for quantifying the amount of fibrosis and pinpointing its location.
“The fibrosis is usually regionalized; it’s not everywhere” in the left atrium, Dr. Kottkamp noted, and the location is very individualized. “You need to look for it in each patient.”
In his experience, about 20% of patients with paroxysmal AF have enough atrial fibrosis to warrant using BIFA along with pulmonary vein isolation. “Among patients with persistent AF, the percentage with significant fibrosis rises to about two-thirds,” Dr. Kottkamp said in an interview. Combining BIFA with pulmonary vein isolation in these patients with higher fibrosis substantially boosts procedural success.
In a recent report, Dr. Kottkamp and his associates presented their experience using BIFA on 92 patients with AF and fibrotic atrial cardiomyopathy. The outcomes showed a relatively high level of success in resolving the AF after an average follow-up of 16 months, with a 69% success rate after a single procedure and an 83% success rate when selected patients received a second BIFA.
Overall, each patient in the series received an average of 1.2 BIFA ablations (J Cardiovasc Electrophysiol. 2017 Sep;28[9]:971-83).
Currently, a limited number of other groups uses BIFA or a similar fibrosis-based ablation approach, and these strategies have not yet undergone prospective assessment in a multicenter study. Despite that, Dr. Kottkamp said he was “confident it will become standard of care.”
Dr. Marrouche has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marreck, Medtronic, Preventice, VytronUS, and Wavelet Health, and he has received research support from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Sciences, and VytronUS. Dr. Kottkamp has been a consultant to Biosense Webster and has been a consultant to and has an equity interest in Kardium.
EXPERT ANALYSIS FROM AF SYMPOSIUM 2018
Characterize duration when seeking etiology of tantrums in children
NEW YORK – Although explosive outbursts or tantrums accompany nearly every psychiatric illness that affects children, the specific features may help identify an etiology, according to Gabrielle A. Carlson, MD.
“There are two components of irritability,” explained Dr. Carlson, professor of psychiatry and pediatrics, Stony Brook (N.Y.) University Medical Center. “One is how often the child loses his or her temper, and the other is what they do when they lose their temper.”
To be useful in identifying the source, the characterization of explosive outbursts must be undertaken in the context of the patient’s history and the duration and types of tantrum-related behaviors, particularly aggressive behavior toward others, according to Dr. Carlson.
Presenting a diagnostic algorithm relevant to children with frequent explosive outbursts, Dr. Carlson suggested that pathways differ for young children and adolescents. Yet, the first step – which is evaluating whether or not irritability is a feature of the patient’s disposition when not in the midst of a tantrum – is common to both groups.
In young children with new onset of explosive outbursts, stressors in school, such as bullying, or family, such as abuse, represent an appropriate initial focus. In adolescents, initial attention should be paid to the potential role of mood disorders, particularly depression, mania, or anxiety, according to Dr. Carlson.
For most patients and most etiologies, tantrums follow a trigger and then resolve quickly. When tantrums do not resolve quickly in patients who remain generally irritable even when they are not having a tantrum, there is an increased likelihood of disruptive mood dysregulation disorder (DMDD).
Relative to tantrums associated with attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), or affective disorders, explosive outbursts associated with DMDD are also more likely to include aggression toward others.
Physical restraint to safeguard the patient or others during a tantrum is uncommon in most conditions associated with tantrums, with the exception of DMDD. Greater aggression tracks with greater DMDD severity. According to data presented by Dr. Carlson, 92% of a clinical sample of DMDD patients exhibited physical aggression, compared with none of those in a community sample.
Tantrums lasting more than 30 minutes were observed in 60% of the clinic sample, versus only 12.5% of the community sample.
Explosive outbursts “are not an uncommon or trivial problem,” according to Dr. Carlson, who cited data suggesting that 70% of children between the ages of 5 and 12 years hospitalized for a psychiatric diseases are referred for an explosive outburst.
She believes that a systematic approach toward characterizing the tantrum will be helpful in understanding the underlying etiology and appropriate treatment. Using such tools as the Irritability and Rages Inventory or the Affective Reactivity Index Child Form, clinicians should seek to evaluate the frequency of tantrums, the duration, and the patient’s symptom burden between tantrums.
If explosive outbursts are rare, they are unlikely to be due to DMDD or affective disorders, such as bipolar disease. If frequent in a patient with chronic psychopathology, those who are generally “fine until frustrated” are the ones more likely to have ADHD or even oppositional defiant disorder (ODD).
The less common profile, which is rage that does not completely resolve, suggests DMDD, a condition that Dr. Carlson described with the mnemonic OI VEY to convey key features. The letters stand for Outbursts that are frequent, Irritable mood in the absence of an outburst, Very chronic (more than 1 per year), Explained by other co-existing conditions, such as mania, and Young (starts between ages 6 and 10 years).
Although tantrums are the way in which children with a broad array of psychiatric conditions express frustration, Dr. Carlson said it is not clear if the mechanisms for irritability and explosive outbursts are shared across conditions. Despite the guidance she offered for linking specific tantrum features with DMDD, she also reiterated that tantrums cannot be considered a symptom specific to any single etiology. The difference between etiologies for irritable children having a tantrum “is not how they feel, the difference is what they do,” Dr. Carlson suggested.
Dr. Carlson reported no relevant financial relationships.
NEW YORK – Although explosive outbursts or tantrums accompany nearly every psychiatric illness that affects children, the specific features may help identify an etiology, according to Gabrielle A. Carlson, MD.
“There are two components of irritability,” explained Dr. Carlson, professor of psychiatry and pediatrics, Stony Brook (N.Y.) University Medical Center. “One is how often the child loses his or her temper, and the other is what they do when they lose their temper.”
To be useful in identifying the source, the characterization of explosive outbursts must be undertaken in the context of the patient’s history and the duration and types of tantrum-related behaviors, particularly aggressive behavior toward others, according to Dr. Carlson.
Presenting a diagnostic algorithm relevant to children with frequent explosive outbursts, Dr. Carlson suggested that pathways differ for young children and adolescents. Yet, the first step – which is evaluating whether or not irritability is a feature of the patient’s disposition when not in the midst of a tantrum – is common to both groups.
In young children with new onset of explosive outbursts, stressors in school, such as bullying, or family, such as abuse, represent an appropriate initial focus. In adolescents, initial attention should be paid to the potential role of mood disorders, particularly depression, mania, or anxiety, according to Dr. Carlson.
For most patients and most etiologies, tantrums follow a trigger and then resolve quickly. When tantrums do not resolve quickly in patients who remain generally irritable even when they are not having a tantrum, there is an increased likelihood of disruptive mood dysregulation disorder (DMDD).
Relative to tantrums associated with attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), or affective disorders, explosive outbursts associated with DMDD are also more likely to include aggression toward others.
Physical restraint to safeguard the patient or others during a tantrum is uncommon in most conditions associated with tantrums, with the exception of DMDD. Greater aggression tracks with greater DMDD severity. According to data presented by Dr. Carlson, 92% of a clinical sample of DMDD patients exhibited physical aggression, compared with none of those in a community sample.
Tantrums lasting more than 30 minutes were observed in 60% of the clinic sample, versus only 12.5% of the community sample.
Explosive outbursts “are not an uncommon or trivial problem,” according to Dr. Carlson, who cited data suggesting that 70% of children between the ages of 5 and 12 years hospitalized for a psychiatric diseases are referred for an explosive outburst.
She believes that a systematic approach toward characterizing the tantrum will be helpful in understanding the underlying etiology and appropriate treatment. Using such tools as the Irritability and Rages Inventory or the Affective Reactivity Index Child Form, clinicians should seek to evaluate the frequency of tantrums, the duration, and the patient’s symptom burden between tantrums.
If explosive outbursts are rare, they are unlikely to be due to DMDD or affective disorders, such as bipolar disease. If frequent in a patient with chronic psychopathology, those who are generally “fine until frustrated” are the ones more likely to have ADHD or even oppositional defiant disorder (ODD).
The less common profile, which is rage that does not completely resolve, suggests DMDD, a condition that Dr. Carlson described with the mnemonic OI VEY to convey key features. The letters stand for Outbursts that are frequent, Irritable mood in the absence of an outburst, Very chronic (more than 1 per year), Explained by other co-existing conditions, such as mania, and Young (starts between ages 6 and 10 years).
Although tantrums are the way in which children with a broad array of psychiatric conditions express frustration, Dr. Carlson said it is not clear if the mechanisms for irritability and explosive outbursts are shared across conditions. Despite the guidance she offered for linking specific tantrum features with DMDD, she also reiterated that tantrums cannot be considered a symptom specific to any single etiology. The difference between etiologies for irritable children having a tantrum “is not how they feel, the difference is what they do,” Dr. Carlson suggested.
Dr. Carlson reported no relevant financial relationships.
NEW YORK – Although explosive outbursts or tantrums accompany nearly every psychiatric illness that affects children, the specific features may help identify an etiology, according to Gabrielle A. Carlson, MD.
“There are two components of irritability,” explained Dr. Carlson, professor of psychiatry and pediatrics, Stony Brook (N.Y.) University Medical Center. “One is how often the child loses his or her temper, and the other is what they do when they lose their temper.”
To be useful in identifying the source, the characterization of explosive outbursts must be undertaken in the context of the patient’s history and the duration and types of tantrum-related behaviors, particularly aggressive behavior toward others, according to Dr. Carlson.
Presenting a diagnostic algorithm relevant to children with frequent explosive outbursts, Dr. Carlson suggested that pathways differ for young children and adolescents. Yet, the first step – which is evaluating whether or not irritability is a feature of the patient’s disposition when not in the midst of a tantrum – is common to both groups.
In young children with new onset of explosive outbursts, stressors in school, such as bullying, or family, such as abuse, represent an appropriate initial focus. In adolescents, initial attention should be paid to the potential role of mood disorders, particularly depression, mania, or anxiety, according to Dr. Carlson.
For most patients and most etiologies, tantrums follow a trigger and then resolve quickly. When tantrums do not resolve quickly in patients who remain generally irritable even when they are not having a tantrum, there is an increased likelihood of disruptive mood dysregulation disorder (DMDD).
Relative to tantrums associated with attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), or affective disorders, explosive outbursts associated with DMDD are also more likely to include aggression toward others.
Physical restraint to safeguard the patient or others during a tantrum is uncommon in most conditions associated with tantrums, with the exception of DMDD. Greater aggression tracks with greater DMDD severity. According to data presented by Dr. Carlson, 92% of a clinical sample of DMDD patients exhibited physical aggression, compared with none of those in a community sample.
Tantrums lasting more than 30 minutes were observed in 60% of the clinic sample, versus only 12.5% of the community sample.
Explosive outbursts “are not an uncommon or trivial problem,” according to Dr. Carlson, who cited data suggesting that 70% of children between the ages of 5 and 12 years hospitalized for a psychiatric diseases are referred for an explosive outburst.
She believes that a systematic approach toward characterizing the tantrum will be helpful in understanding the underlying etiology and appropriate treatment. Using such tools as the Irritability and Rages Inventory or the Affective Reactivity Index Child Form, clinicians should seek to evaluate the frequency of tantrums, the duration, and the patient’s symptom burden between tantrums.
If explosive outbursts are rare, they are unlikely to be due to DMDD or affective disorders, such as bipolar disease. If frequent in a patient with chronic psychopathology, those who are generally “fine until frustrated” are the ones more likely to have ADHD or even oppositional defiant disorder (ODD).
The less common profile, which is rage that does not completely resolve, suggests DMDD, a condition that Dr. Carlson described with the mnemonic OI VEY to convey key features. The letters stand for Outbursts that are frequent, Irritable mood in the absence of an outburst, Very chronic (more than 1 per year), Explained by other co-existing conditions, such as mania, and Young (starts between ages 6 and 10 years).
Although tantrums are the way in which children with a broad array of psychiatric conditions express frustration, Dr. Carlson said it is not clear if the mechanisms for irritability and explosive outbursts are shared across conditions. Despite the guidance she offered for linking specific tantrum features with DMDD, she also reiterated that tantrums cannot be considered a symptom specific to any single etiology. The difference between etiologies for irritable children having a tantrum “is not how they feel, the difference is what they do,” Dr. Carlson suggested.
Dr. Carlson reported no relevant financial relationships.
REPORTING FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Want to expand aesthetic dermatology business? Appeal to men
MIAMI – Bringing more men into an aesthetic dermatology practice can expand the patient population, increase business revenue, and pay long-term dividends in terms of patient loyalty and repeat business.
But men aren’t like women when it comes to aesthetic concerns, so the strategies used to market your aesthetic offerings to female patients might miss the mark with men, cautioned Terrence Keaney, MD.
“I spend more time explaining therapies and what might be best for them,” he noted. “I explain the scientific rationale and treatment mechanisms so they will be more comfortable.” Making sure they understand is important, because “men often nod and don’t ask questions.”
The extra effort up front can pay off.
“The beauty of men is when they get a great result and are happy with you, men are very physician loyal. Once they get a great result, they’re yours forever,” said Dr. Keaney, an assistant clinical professor of dermatology at George Washington University, Washington, and a private practice dermatologist in Arlington, Va.
Cost is the leading deterrent for men to embrace aesthetic procedures, a factor that also ranks first among women. Men are also concerned that results will not look natural and want information about safety and side effects, Dr. Keaney said. “These deterrents can be overcome with proper education and counseling.”
Marketing to men is different
Although growing a male anesthetic patient base is more difficult, Dr. Keaney recommends it, especially for dermatology practices in a competitive market.
This tactic of targeting untapped markets to grow a business, rather than competing on the same level as everyone else, is outlined in a book he recommends, “Blue Ocean Strategy,” by W. Chan Kim and Renée Mauborgne. “It’s about unlocking new demand, and I will argue that, in aesthetic medicine, it’s those male patients.”
“The male aesthetic market is truly untapped and shows tremendous growth potential,” Dr. Keaney said. “Particularly as millennials age, the demand for cosmetic procedures in men will only increase.”
A first step is to make male aesthetic patients feel welcome and comfortable. “Think about a reluctant male patient walking into your office; it can be intimidating if the staff and everyone in the waiting room is female,” Dr. Keaney said. “But you don’t need to put a keg in the corner, either.” He added more wood and changed the colors of his office, for example.
Don’t go overboard
Marketing aesthetic services to men is also different, a lesson Dr. Keaney learned from the outset.
“When I first started a practice, I wanted to attract more male cosmetic patients, and I decided to throw a male cosmetics seminar,” he recalled. “I thought it would be a great opportunity to educate them.”
He partnered with a plastic surgeon, rented a ballroom, sent out an e-blast, and mailed flyers. “We had zero RSVPs. We canceled it.”
He added, “Men are not sitting at the computer thinking, ‘I wish someone would throw a seminar on aesthetics.’”
A better strategy came the following year as a men’s health event with a broader scope. A urologist, internist, dermatologist, and plastic surgeon talked about a variety of health issues. “They were blown away by the options from the dermatologist and the plastic surgeon.”
A growing market
An American Society for Dermatologic Surgery annual survey reveals dermatologic surgeons performed nearly 10.5 million medically necessary and cosmetic procedures in 2016, the latest year for which results are available. The rate is up 5% from the year before, and up by more than 30%, compared with 2012.
“Within the growth of procedures performed, the male and millennial demographics’ interest in cosmetic treatments also continues to rise,” the survey authors noted. “In the last 5 years, men receiving wrinkle relaxers has increased 9%, and men using soft-tissue fillers grew from 2% to 9%.” The survey also reveals that patients younger than 30 years are seeking more cosmetic treatments. In fact, millennials’ use of wrinkle relaxers increased 20% from 2015, and 50% since 2012.
Address the top male aesthetic concerns
Men are interested in looking healthy, young, and staying fit, Dr. Keaney said, but there is often a disconnect in the male market. “I would argue the real rate limiter is education,” he explained, “and that both the industry and physicians are at fault.”
Most messages about aesthetic procedures have not been targeted toward men. For example, only 39% of 600 aesthetically inclined men knew about dermal fillers in a study Dr. Keaney co-authored (Dermatol Surg. 2016 Oct;42[10]:1155-63).
“I talk to men in my practice about dermal fillers, and most think they’re only for injection in the lips,” he said. The results of the online survey came from men “cosmetically on the cusp,” as he described them – men familiar with neuromodulators for facial rejuvenation, but who had never tried such a therapy.
Tear troughs, double chin, crow’s feet, and forehead lines were the most common concerns, in order, reported by study participants. Dr. Keaney said. “You’ll notice what is missing here: the cheeks, the nasolabial folds, and the lips. And what are those? The FDA-approved indications for dermal fillers.”
Even though it doesn’t top the list of men’s concerns in this study, overall, “if you’re looking to grow your male aesthetic patient population, the number one cosmetic concern among men remains hair loss,” noted Dr. Keaney. “You cannot ignore hair loss. It has a large psychosocial impact.”
During a full-body exam, Dr. Keaney recommends using a scalp exam as an opportunity to ask about any hair-loss concerns.
Encouraging signs from other industries
Other industries are showing a rise in the appearance-conscious male consumer, Dr. Keaney said. Men’s skin care, grooming, and luxury fashion industries are all growing, for example.
Worldwide, the personal care market for men is forecast to grow to $166 billion globally by 2022, according to a report from Allied Market Research. The compound average growth rate is expected to grow more than 5% each year between now and then.
“Men are spending money on their hair and skin,” Dr. Keaney said. “The question is, Why aren’t they spending money on their face? It’s how we interact with the world.”
Dr. Keaney has served on the advisory board of, consulted for, and was a speaker for Allergan. He was also a speaker for Eclipse, Sciton, and Syneron Candela, and served on the advisory boards for Aclaris and Merz.
MIAMI – Bringing more men into an aesthetic dermatology practice can expand the patient population, increase business revenue, and pay long-term dividends in terms of patient loyalty and repeat business.
But men aren’t like women when it comes to aesthetic concerns, so the strategies used to market your aesthetic offerings to female patients might miss the mark with men, cautioned Terrence Keaney, MD.
“I spend more time explaining therapies and what might be best for them,” he noted. “I explain the scientific rationale and treatment mechanisms so they will be more comfortable.” Making sure they understand is important, because “men often nod and don’t ask questions.”
The extra effort up front can pay off.
“The beauty of men is when they get a great result and are happy with you, men are very physician loyal. Once they get a great result, they’re yours forever,” said Dr. Keaney, an assistant clinical professor of dermatology at George Washington University, Washington, and a private practice dermatologist in Arlington, Va.
Cost is the leading deterrent for men to embrace aesthetic procedures, a factor that also ranks first among women. Men are also concerned that results will not look natural and want information about safety and side effects, Dr. Keaney said. “These deterrents can be overcome with proper education and counseling.”
Marketing to men is different
Although growing a male anesthetic patient base is more difficult, Dr. Keaney recommends it, especially for dermatology practices in a competitive market.
This tactic of targeting untapped markets to grow a business, rather than competing on the same level as everyone else, is outlined in a book he recommends, “Blue Ocean Strategy,” by W. Chan Kim and Renée Mauborgne. “It’s about unlocking new demand, and I will argue that, in aesthetic medicine, it’s those male patients.”
“The male aesthetic market is truly untapped and shows tremendous growth potential,” Dr. Keaney said. “Particularly as millennials age, the demand for cosmetic procedures in men will only increase.”
A first step is to make male aesthetic patients feel welcome and comfortable. “Think about a reluctant male patient walking into your office; it can be intimidating if the staff and everyone in the waiting room is female,” Dr. Keaney said. “But you don’t need to put a keg in the corner, either.” He added more wood and changed the colors of his office, for example.
Don’t go overboard
Marketing aesthetic services to men is also different, a lesson Dr. Keaney learned from the outset.
“When I first started a practice, I wanted to attract more male cosmetic patients, and I decided to throw a male cosmetics seminar,” he recalled. “I thought it would be a great opportunity to educate them.”
He partnered with a plastic surgeon, rented a ballroom, sent out an e-blast, and mailed flyers. “We had zero RSVPs. We canceled it.”
He added, “Men are not sitting at the computer thinking, ‘I wish someone would throw a seminar on aesthetics.’”
A better strategy came the following year as a men’s health event with a broader scope. A urologist, internist, dermatologist, and plastic surgeon talked about a variety of health issues. “They were blown away by the options from the dermatologist and the plastic surgeon.”
A growing market
An American Society for Dermatologic Surgery annual survey reveals dermatologic surgeons performed nearly 10.5 million medically necessary and cosmetic procedures in 2016, the latest year for which results are available. The rate is up 5% from the year before, and up by more than 30%, compared with 2012.
“Within the growth of procedures performed, the male and millennial demographics’ interest in cosmetic treatments also continues to rise,” the survey authors noted. “In the last 5 years, men receiving wrinkle relaxers has increased 9%, and men using soft-tissue fillers grew from 2% to 9%.” The survey also reveals that patients younger than 30 years are seeking more cosmetic treatments. In fact, millennials’ use of wrinkle relaxers increased 20% from 2015, and 50% since 2012.
Address the top male aesthetic concerns
Men are interested in looking healthy, young, and staying fit, Dr. Keaney said, but there is often a disconnect in the male market. “I would argue the real rate limiter is education,” he explained, “and that both the industry and physicians are at fault.”
Most messages about aesthetic procedures have not been targeted toward men. For example, only 39% of 600 aesthetically inclined men knew about dermal fillers in a study Dr. Keaney co-authored (Dermatol Surg. 2016 Oct;42[10]:1155-63).
“I talk to men in my practice about dermal fillers, and most think they’re only for injection in the lips,” he said. The results of the online survey came from men “cosmetically on the cusp,” as he described them – men familiar with neuromodulators for facial rejuvenation, but who had never tried such a therapy.
Tear troughs, double chin, crow’s feet, and forehead lines were the most common concerns, in order, reported by study participants. Dr. Keaney said. “You’ll notice what is missing here: the cheeks, the nasolabial folds, and the lips. And what are those? The FDA-approved indications for dermal fillers.”
Even though it doesn’t top the list of men’s concerns in this study, overall, “if you’re looking to grow your male aesthetic patient population, the number one cosmetic concern among men remains hair loss,” noted Dr. Keaney. “You cannot ignore hair loss. It has a large psychosocial impact.”
During a full-body exam, Dr. Keaney recommends using a scalp exam as an opportunity to ask about any hair-loss concerns.
Encouraging signs from other industries
Other industries are showing a rise in the appearance-conscious male consumer, Dr. Keaney said. Men’s skin care, grooming, and luxury fashion industries are all growing, for example.
Worldwide, the personal care market for men is forecast to grow to $166 billion globally by 2022, according to a report from Allied Market Research. The compound average growth rate is expected to grow more than 5% each year between now and then.
“Men are spending money on their hair and skin,” Dr. Keaney said. “The question is, Why aren’t they spending money on their face? It’s how we interact with the world.”
Dr. Keaney has served on the advisory board of, consulted for, and was a speaker for Allergan. He was also a speaker for Eclipse, Sciton, and Syneron Candela, and served on the advisory boards for Aclaris and Merz.
MIAMI – Bringing more men into an aesthetic dermatology practice can expand the patient population, increase business revenue, and pay long-term dividends in terms of patient loyalty and repeat business.
But men aren’t like women when it comes to aesthetic concerns, so the strategies used to market your aesthetic offerings to female patients might miss the mark with men, cautioned Terrence Keaney, MD.
“I spend more time explaining therapies and what might be best for them,” he noted. “I explain the scientific rationale and treatment mechanisms so they will be more comfortable.” Making sure they understand is important, because “men often nod and don’t ask questions.”
The extra effort up front can pay off.
“The beauty of men is when they get a great result and are happy with you, men are very physician loyal. Once they get a great result, they’re yours forever,” said Dr. Keaney, an assistant clinical professor of dermatology at George Washington University, Washington, and a private practice dermatologist in Arlington, Va.
Cost is the leading deterrent for men to embrace aesthetic procedures, a factor that also ranks first among women. Men are also concerned that results will not look natural and want information about safety and side effects, Dr. Keaney said. “These deterrents can be overcome with proper education and counseling.”
Marketing to men is different
Although growing a male anesthetic patient base is more difficult, Dr. Keaney recommends it, especially for dermatology practices in a competitive market.
This tactic of targeting untapped markets to grow a business, rather than competing on the same level as everyone else, is outlined in a book he recommends, “Blue Ocean Strategy,” by W. Chan Kim and Renée Mauborgne. “It’s about unlocking new demand, and I will argue that, in aesthetic medicine, it’s those male patients.”
“The male aesthetic market is truly untapped and shows tremendous growth potential,” Dr. Keaney said. “Particularly as millennials age, the demand for cosmetic procedures in men will only increase.”
A first step is to make male aesthetic patients feel welcome and comfortable. “Think about a reluctant male patient walking into your office; it can be intimidating if the staff and everyone in the waiting room is female,” Dr. Keaney said. “But you don’t need to put a keg in the corner, either.” He added more wood and changed the colors of his office, for example.
Don’t go overboard
Marketing aesthetic services to men is also different, a lesson Dr. Keaney learned from the outset.
“When I first started a practice, I wanted to attract more male cosmetic patients, and I decided to throw a male cosmetics seminar,” he recalled. “I thought it would be a great opportunity to educate them.”
He partnered with a plastic surgeon, rented a ballroom, sent out an e-blast, and mailed flyers. “We had zero RSVPs. We canceled it.”
He added, “Men are not sitting at the computer thinking, ‘I wish someone would throw a seminar on aesthetics.’”
A better strategy came the following year as a men’s health event with a broader scope. A urologist, internist, dermatologist, and plastic surgeon talked about a variety of health issues. “They were blown away by the options from the dermatologist and the plastic surgeon.”
A growing market
An American Society for Dermatologic Surgery annual survey reveals dermatologic surgeons performed nearly 10.5 million medically necessary and cosmetic procedures in 2016, the latest year for which results are available. The rate is up 5% from the year before, and up by more than 30%, compared with 2012.
“Within the growth of procedures performed, the male and millennial demographics’ interest in cosmetic treatments also continues to rise,” the survey authors noted. “In the last 5 years, men receiving wrinkle relaxers has increased 9%, and men using soft-tissue fillers grew from 2% to 9%.” The survey also reveals that patients younger than 30 years are seeking more cosmetic treatments. In fact, millennials’ use of wrinkle relaxers increased 20% from 2015, and 50% since 2012.
Address the top male aesthetic concerns
Men are interested in looking healthy, young, and staying fit, Dr. Keaney said, but there is often a disconnect in the male market. “I would argue the real rate limiter is education,” he explained, “and that both the industry and physicians are at fault.”
Most messages about aesthetic procedures have not been targeted toward men. For example, only 39% of 600 aesthetically inclined men knew about dermal fillers in a study Dr. Keaney co-authored (Dermatol Surg. 2016 Oct;42[10]:1155-63).
“I talk to men in my practice about dermal fillers, and most think they’re only for injection in the lips,” he said. The results of the online survey came from men “cosmetically on the cusp,” as he described them – men familiar with neuromodulators for facial rejuvenation, but who had never tried such a therapy.
Tear troughs, double chin, crow’s feet, and forehead lines were the most common concerns, in order, reported by study participants. Dr. Keaney said. “You’ll notice what is missing here: the cheeks, the nasolabial folds, and the lips. And what are those? The FDA-approved indications for dermal fillers.”
Even though it doesn’t top the list of men’s concerns in this study, overall, “if you’re looking to grow your male aesthetic patient population, the number one cosmetic concern among men remains hair loss,” noted Dr. Keaney. “You cannot ignore hair loss. It has a large psychosocial impact.”
During a full-body exam, Dr. Keaney recommends using a scalp exam as an opportunity to ask about any hair-loss concerns.
Encouraging signs from other industries
Other industries are showing a rise in the appearance-conscious male consumer, Dr. Keaney said. Men’s skin care, grooming, and luxury fashion industries are all growing, for example.
Worldwide, the personal care market for men is forecast to grow to $166 billion globally by 2022, according to a report from Allied Market Research. The compound average growth rate is expected to grow more than 5% each year between now and then.
“Men are spending money on their hair and skin,” Dr. Keaney said. “The question is, Why aren’t they spending money on their face? It’s how we interact with the world.”
Dr. Keaney has served on the advisory board of, consulted for, and was a speaker for Allergan. He was also a speaker for Eclipse, Sciton, and Syneron Candela, and served on the advisory boards for Aclaris and Merz.
REPORTING FROM ODAC 2018
Learn ‘four Ds’ approach to heart failure in diabetes
LOS ANGELES – , such as lung cancer, because diabetes makes the pathophysiology of heart failure worse, according to Mark Kearney, MD.
“Diabetes amplifies the neurohormonal response to heart failure, so it drives progressive heart failure and increases the risk for sudden death,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “As left ventricular function goes down, patients with diabetes have heightened activation of the renin angiotensin system. They have increased left ventricular hypertrophy, and they have increased sympathetic nervous system activation.”
Dr. Kearney, a cardiologist who directs the Leeds Institute of Cardiovascular & Metabolic Medicine at Leeds (England) University, offered a “four Ds” framework that clinicians can use to improve prognosis in these patients.
1. Use a loop diuretic to control symptoms. “If the patient has fluid retention, it’s important to get them out of congestive cardiac syndrome as quickly as possible,” he said.
2. Disease modification with beta-blockers and ACE inhibitors, to the maximal dose tolerated. “These are still the mainstays of treatment for patients with heart failure, and they’re even more important in patients with diabetes and heart failure,” he said.
3. Consider device therapy, including defibrillators and resynchronization therapy.4. Optimize diabetes management.
“If you keep these things in your mind as you see a patient with heart failure and diabetes, it will give you a guide to approaching these patients,” said Dr. Kearney, who is also research lead for heart failure services at the University of Leeds. “When I see patients, I’ll check for edema right away. If they have it, I’ll increase the diuretic, and I’ll think about the different steps in the treatment pathway.”
He described heart failure due to systolic dysfunction as a reduction in cardiac output that doesn’t meet the demands of the body, the endpoint of a whole range of insults to the left ventricle.
“The most common cause today is ischemic heart disease; it used to be hypertension,” he said. “People over 40 have a one in five chance of developing heart failure, so it’s really important for all of us to improve outcomes in this terrible syndrome.”
According to a study of nearly 2,000 unselected patients conducted by Dr. Kearney and his associates, those with diabetes and heart failure are more likely to have ischemia, compared with those who have heart failure and no diabetes (75% vs. 58%, respectively), lower hemoglobin (13 g/dL vs. 13.7 g/dL), and worse renal function (eGFR of 51 mL/min per 1.732 m2 vs 57 mL/min per 1.732 m2) (Diab Vasc Dis Res. 2013 Jul;10[4]:330-6).
He added that type 2 diabetes is a sudden death risk equivalent to patients with ischemic heart disease and left ventricular systolic dysfunction (Heart 2016 May 15;102[10]:735-40).
“So, if you have diabetes and the U.K. National Institute for Health and Care Excellence guidelines indication for a defibrillator, your risk of sudden death in 5 years is probably 50%,” Dr. Kearney said. “The best treatment in this case is a prophylactic defibrillator.”
ACE inhibitors are used to protect these patients against cardiac myocyte cell death and vasoconstriction, while beta-blockers are used to protect against the activation of the sympathetic nervous system.
“Often, patients don’t like taking beta-blockers because they say they make them feel tired – when in fact they don’t realize it’s their heart failure that’s making them feel tired,” Dr. Kearney said.
He and his associates examined the effect of different drugs doses on all-cause mortality at 5 years. They found that, among patients with heart failure, reduced ejection fraction, and no diabetes, ramipril conferred a 3% improvement in mortality per milligram. At the same time, the mortality among patients with diabetes and heart failure who did not receive a beta-blocker was about 7%.
However, the absolute gain from beta-blocker use in patients with diabetes and heart failure was three times that of patients without diabetes.
“So, every milligram you increase the dose by, there’s an associated improvement in risk,” Dr. Kearney said. “Over 5 years, comparing the lowest beta-blocker dose to the highest beta-blocker dose, it was 1 year of life gained. So, when I see my patients and they ask about side effects of beta-blockers, I now say to them, ‘The side effects actually make you live longer.’”
He concluded his remarks by noting that while he is not a diabetes expert, it’s clear that diabetes is intimately linked to the pathophysiology of heart failure.
“If you’re insulin resistant, you have hypertension, hyperglycemia, you have inflammation and bone marrow dysfunction – all of which can exacerbate left ventricle dysfunction,” he said. “You have a syndrome in which you have cardiac dysfunction and metabolic dysfunction that conspire to lead to worsening of left ventricular dysfunction.”
Dr. Kearney disclosed that he has been a speaker for Merck.
LOS ANGELES – , such as lung cancer, because diabetes makes the pathophysiology of heart failure worse, according to Mark Kearney, MD.
“Diabetes amplifies the neurohormonal response to heart failure, so it drives progressive heart failure and increases the risk for sudden death,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “As left ventricular function goes down, patients with diabetes have heightened activation of the renin angiotensin system. They have increased left ventricular hypertrophy, and they have increased sympathetic nervous system activation.”
Dr. Kearney, a cardiologist who directs the Leeds Institute of Cardiovascular & Metabolic Medicine at Leeds (England) University, offered a “four Ds” framework that clinicians can use to improve prognosis in these patients.
1. Use a loop diuretic to control symptoms. “If the patient has fluid retention, it’s important to get them out of congestive cardiac syndrome as quickly as possible,” he said.
2. Disease modification with beta-blockers and ACE inhibitors, to the maximal dose tolerated. “These are still the mainstays of treatment for patients with heart failure, and they’re even more important in patients with diabetes and heart failure,” he said.
3. Consider device therapy, including defibrillators and resynchronization therapy.4. Optimize diabetes management.
“If you keep these things in your mind as you see a patient with heart failure and diabetes, it will give you a guide to approaching these patients,” said Dr. Kearney, who is also research lead for heart failure services at the University of Leeds. “When I see patients, I’ll check for edema right away. If they have it, I’ll increase the diuretic, and I’ll think about the different steps in the treatment pathway.”
He described heart failure due to systolic dysfunction as a reduction in cardiac output that doesn’t meet the demands of the body, the endpoint of a whole range of insults to the left ventricle.
“The most common cause today is ischemic heart disease; it used to be hypertension,” he said. “People over 40 have a one in five chance of developing heart failure, so it’s really important for all of us to improve outcomes in this terrible syndrome.”
According to a study of nearly 2,000 unselected patients conducted by Dr. Kearney and his associates, those with diabetes and heart failure are more likely to have ischemia, compared with those who have heart failure and no diabetes (75% vs. 58%, respectively), lower hemoglobin (13 g/dL vs. 13.7 g/dL), and worse renal function (eGFR of 51 mL/min per 1.732 m2 vs 57 mL/min per 1.732 m2) (Diab Vasc Dis Res. 2013 Jul;10[4]:330-6).
He added that type 2 diabetes is a sudden death risk equivalent to patients with ischemic heart disease and left ventricular systolic dysfunction (Heart 2016 May 15;102[10]:735-40).
“So, if you have diabetes and the U.K. National Institute for Health and Care Excellence guidelines indication for a defibrillator, your risk of sudden death in 5 years is probably 50%,” Dr. Kearney said. “The best treatment in this case is a prophylactic defibrillator.”
ACE inhibitors are used to protect these patients against cardiac myocyte cell death and vasoconstriction, while beta-blockers are used to protect against the activation of the sympathetic nervous system.
“Often, patients don’t like taking beta-blockers because they say they make them feel tired – when in fact they don’t realize it’s their heart failure that’s making them feel tired,” Dr. Kearney said.
He and his associates examined the effect of different drugs doses on all-cause mortality at 5 years. They found that, among patients with heart failure, reduced ejection fraction, and no diabetes, ramipril conferred a 3% improvement in mortality per milligram. At the same time, the mortality among patients with diabetes and heart failure who did not receive a beta-blocker was about 7%.
However, the absolute gain from beta-blocker use in patients with diabetes and heart failure was three times that of patients without diabetes.
“So, every milligram you increase the dose by, there’s an associated improvement in risk,” Dr. Kearney said. “Over 5 years, comparing the lowest beta-blocker dose to the highest beta-blocker dose, it was 1 year of life gained. So, when I see my patients and they ask about side effects of beta-blockers, I now say to them, ‘The side effects actually make you live longer.’”
He concluded his remarks by noting that while he is not a diabetes expert, it’s clear that diabetes is intimately linked to the pathophysiology of heart failure.
“If you’re insulin resistant, you have hypertension, hyperglycemia, you have inflammation and bone marrow dysfunction – all of which can exacerbate left ventricle dysfunction,” he said. “You have a syndrome in which you have cardiac dysfunction and metabolic dysfunction that conspire to lead to worsening of left ventricular dysfunction.”
Dr. Kearney disclosed that he has been a speaker for Merck.
LOS ANGELES – , such as lung cancer, because diabetes makes the pathophysiology of heart failure worse, according to Mark Kearney, MD.
“Diabetes amplifies the neurohormonal response to heart failure, so it drives progressive heart failure and increases the risk for sudden death,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “As left ventricular function goes down, patients with diabetes have heightened activation of the renin angiotensin system. They have increased left ventricular hypertrophy, and they have increased sympathetic nervous system activation.”
Dr. Kearney, a cardiologist who directs the Leeds Institute of Cardiovascular & Metabolic Medicine at Leeds (England) University, offered a “four Ds” framework that clinicians can use to improve prognosis in these patients.
1. Use a loop diuretic to control symptoms. “If the patient has fluid retention, it’s important to get them out of congestive cardiac syndrome as quickly as possible,” he said.
2. Disease modification with beta-blockers and ACE inhibitors, to the maximal dose tolerated. “These are still the mainstays of treatment for patients with heart failure, and they’re even more important in patients with diabetes and heart failure,” he said.
3. Consider device therapy, including defibrillators and resynchronization therapy.4. Optimize diabetes management.
“If you keep these things in your mind as you see a patient with heart failure and diabetes, it will give you a guide to approaching these patients,” said Dr. Kearney, who is also research lead for heart failure services at the University of Leeds. “When I see patients, I’ll check for edema right away. If they have it, I’ll increase the diuretic, and I’ll think about the different steps in the treatment pathway.”
He described heart failure due to systolic dysfunction as a reduction in cardiac output that doesn’t meet the demands of the body, the endpoint of a whole range of insults to the left ventricle.
“The most common cause today is ischemic heart disease; it used to be hypertension,” he said. “People over 40 have a one in five chance of developing heart failure, so it’s really important for all of us to improve outcomes in this terrible syndrome.”
According to a study of nearly 2,000 unselected patients conducted by Dr. Kearney and his associates, those with diabetes and heart failure are more likely to have ischemia, compared with those who have heart failure and no diabetes (75% vs. 58%, respectively), lower hemoglobin (13 g/dL vs. 13.7 g/dL), and worse renal function (eGFR of 51 mL/min per 1.732 m2 vs 57 mL/min per 1.732 m2) (Diab Vasc Dis Res. 2013 Jul;10[4]:330-6).
He added that type 2 diabetes is a sudden death risk equivalent to patients with ischemic heart disease and left ventricular systolic dysfunction (Heart 2016 May 15;102[10]:735-40).
“So, if you have diabetes and the U.K. National Institute for Health and Care Excellence guidelines indication for a defibrillator, your risk of sudden death in 5 years is probably 50%,” Dr. Kearney said. “The best treatment in this case is a prophylactic defibrillator.”
ACE inhibitors are used to protect these patients against cardiac myocyte cell death and vasoconstriction, while beta-blockers are used to protect against the activation of the sympathetic nervous system.
“Often, patients don’t like taking beta-blockers because they say they make them feel tired – when in fact they don’t realize it’s their heart failure that’s making them feel tired,” Dr. Kearney said.
He and his associates examined the effect of different drugs doses on all-cause mortality at 5 years. They found that, among patients with heart failure, reduced ejection fraction, and no diabetes, ramipril conferred a 3% improvement in mortality per milligram. At the same time, the mortality among patients with diabetes and heart failure who did not receive a beta-blocker was about 7%.
However, the absolute gain from beta-blocker use in patients with diabetes and heart failure was three times that of patients without diabetes.
“So, every milligram you increase the dose by, there’s an associated improvement in risk,” Dr. Kearney said. “Over 5 years, comparing the lowest beta-blocker dose to the highest beta-blocker dose, it was 1 year of life gained. So, when I see my patients and they ask about side effects of beta-blockers, I now say to them, ‘The side effects actually make you live longer.’”
He concluded his remarks by noting that while he is not a diabetes expert, it’s clear that diabetes is intimately linked to the pathophysiology of heart failure.
“If you’re insulin resistant, you have hypertension, hyperglycemia, you have inflammation and bone marrow dysfunction – all of which can exacerbate left ventricle dysfunction,” he said. “You have a syndrome in which you have cardiac dysfunction and metabolic dysfunction that conspire to lead to worsening of left ventricular dysfunction.”
Dr. Kearney disclosed that he has been a speaker for Merck.
EXPERT ANALYSIS FROM WCIRDC 2017
Whatever the substance, adolescents’ abuse shares common links
SAN DIEGO – Among adolescent daily cigarette smokers, the individual and concomitant use of alcohol, marijuana, and tobacco have unique and common associations with reinforcement sensitivity, with negative affect, and with electrophysiological signatures of reward function, results from a novel study demonstrated.
“The co-use of alcohol, marijuana, and tobacco in youth are associated bidirectionally with higher rates of substance use, higher levels of addiction severity, and with poorer treatment outcomes for youth who present for treatment,” lead study author Christopher J. Hammond, MD, said at the annual meeting and scientific symposium of the American Academy of Addiction Psychiatry.
Currently, the effects of combined alcohol, marijuana, and tobacco use on brain function are poorly understood, noted Dr. Hammond of the division of child and adolescent psychiatry at Johns Hopkins Bayview Medical Center, Baltimore.
Published studies to date suggest that alcohol, marijuana, and tobacco use disorders are linked separately to dysfunction in the neural substrates of reward and punishment processing, but none has examined co-use or comorbid disorders in adolescents.
In a cross-sectional, single-visit study, Dr. Hammond and his associates examined a population of 36 adolescent non-deprived daily cigarette smokers and 29 healthy controls from the greater New Haven, Conn., area, matched for age, gender, and grade level. The subjects ranged in age from 14 to 20 years and were administered self-report measures characterizing tobacco, marijuana, and alcohol use. The researchers also collected urine and breathalyzer measures to characterize tobacco and cannabis use.
All subjects completed a number of self-report questionnaires characterizing their substance use patterns, their addiction severity, impulsivity, sensitivity to reward and punishment, and depression. They also underwent a 45-minute EEG, during which they completed a resting EEG test and completed a reward task.
The adolescent daily cigarette smoker group had blunted or decreased sensitivity to punishment and increased impulsivity, compared with the healthy controls, Dr. Hammond reported.
Co-occurring drug use was high in the adolescent daily smoker group, with 80% reporting heavy marijuana use (defined as using it over 100 times during adolescence), and 67% reporting heavy episodic binge drinking (defined as consuming greater than four alcoholic beverages for females during one sitting and greater than five for males at least two or more times a month).
One out of two of the daily cigarette smokers were also daily marijuana smokers, and about 75% of the adolescent smokers had a positive urine drug screen for marijuana. They smoked an average of eight cigarettes per day, used cannabis about 17 days out of the month, and they had about 1.5 binge drinking episodes per month.
Next, the researchers used linear regression analyses to examine which of the psychological variables were associated with alcohol, marijuana, and tobacco use severity within the smoker group, after co-varying for age, gender, race/ethnicity, and full-scale IQ.
“For alcohol use, we found that depression, sensitivity to reward, and impulsivity were significantly associated with alcohol problem severity scores, even after controlling for sociodemographics and other drug use (P less than .05),” Dr. Hammond said.
“For marijuana use, we found that sensitivity to reward and impulsivity were significantly associated with cannabis problem severity, even after controlling for demographics and alcohol and other drug use (P less than .01),” he continued. “For tobacco use, we found that anxiety sensitivity was significantly associated with nicotine dependence scores, even after controlling for demographics and alcohol and marijuana use (P less than .001).”
On EEG analyses, the researchers found no main effects for group or group by condition for the feedback-related negativity (FRN) signal or for the event-related Theta oscillation between the adolescent non-deprived smokers and the healthy controls.
However, examination of the smoker subgroups revealed a unique and shared association between alcohol, marijuana, and tobacco and the EEG signals.
“With regard to substance use associations with the FRN smokers, regression analyses showed that cannabis use problem severity was associated with an increased FRN amplitude during the reward condition only,” Dr. Hammond said. “This finding remained significant after co-varying for demographics, for other drug use, for nicotine dependence and alcohol severity as well.
“We also found an association between alcohol problem severity and mean FRN amplitude, but with no differences across conditions,” he added. There was an association also “ between nicotine dependence and decreased FRN latency, but only during the reward and draw conditions, suggesting a nicotine severity association with speed of processing salient reward and stimuli.”
While the findings need to be better studied and replicated, “these associations may be leveraged to better personalize our interventions for these different substances of abuse,” Dr. Hammond observed. “The study also provides preliminary evidence for a dual-process model of substance use, specifically for cannabis. Cannabis severity in adolescent smokers is associated with increased bottom-up reward signaling and impaired top-down cognitive control over a salient or rewarding stimulus.”
The study was supported by the American Academy of Child and Adolescent Psychiatry and the National Institute on Drug Abuse. Dr. Hammond disclosed that he receives research funding from both organizations.
SOURCE: Hammond et al. AAAP 2017. Paper session A3.
SAN DIEGO – Among adolescent daily cigarette smokers, the individual and concomitant use of alcohol, marijuana, and tobacco have unique and common associations with reinforcement sensitivity, with negative affect, and with electrophysiological signatures of reward function, results from a novel study demonstrated.
“The co-use of alcohol, marijuana, and tobacco in youth are associated bidirectionally with higher rates of substance use, higher levels of addiction severity, and with poorer treatment outcomes for youth who present for treatment,” lead study author Christopher J. Hammond, MD, said at the annual meeting and scientific symposium of the American Academy of Addiction Psychiatry.
Currently, the effects of combined alcohol, marijuana, and tobacco use on brain function are poorly understood, noted Dr. Hammond of the division of child and adolescent psychiatry at Johns Hopkins Bayview Medical Center, Baltimore.
Published studies to date suggest that alcohol, marijuana, and tobacco use disorders are linked separately to dysfunction in the neural substrates of reward and punishment processing, but none has examined co-use or comorbid disorders in adolescents.
In a cross-sectional, single-visit study, Dr. Hammond and his associates examined a population of 36 adolescent non-deprived daily cigarette smokers and 29 healthy controls from the greater New Haven, Conn., area, matched for age, gender, and grade level. The subjects ranged in age from 14 to 20 years and were administered self-report measures characterizing tobacco, marijuana, and alcohol use. The researchers also collected urine and breathalyzer measures to characterize tobacco and cannabis use.
All subjects completed a number of self-report questionnaires characterizing their substance use patterns, their addiction severity, impulsivity, sensitivity to reward and punishment, and depression. They also underwent a 45-minute EEG, during which they completed a resting EEG test and completed a reward task.
The adolescent daily cigarette smoker group had blunted or decreased sensitivity to punishment and increased impulsivity, compared with the healthy controls, Dr. Hammond reported.
Co-occurring drug use was high in the adolescent daily smoker group, with 80% reporting heavy marijuana use (defined as using it over 100 times during adolescence), and 67% reporting heavy episodic binge drinking (defined as consuming greater than four alcoholic beverages for females during one sitting and greater than five for males at least two or more times a month).
One out of two of the daily cigarette smokers were also daily marijuana smokers, and about 75% of the adolescent smokers had a positive urine drug screen for marijuana. They smoked an average of eight cigarettes per day, used cannabis about 17 days out of the month, and they had about 1.5 binge drinking episodes per month.
Next, the researchers used linear regression analyses to examine which of the psychological variables were associated with alcohol, marijuana, and tobacco use severity within the smoker group, after co-varying for age, gender, race/ethnicity, and full-scale IQ.
“For alcohol use, we found that depression, sensitivity to reward, and impulsivity were significantly associated with alcohol problem severity scores, even after controlling for sociodemographics and other drug use (P less than .05),” Dr. Hammond said.
“For marijuana use, we found that sensitivity to reward and impulsivity were significantly associated with cannabis problem severity, even after controlling for demographics and alcohol and other drug use (P less than .01),” he continued. “For tobacco use, we found that anxiety sensitivity was significantly associated with nicotine dependence scores, even after controlling for demographics and alcohol and marijuana use (P less than .001).”
On EEG analyses, the researchers found no main effects for group or group by condition for the feedback-related negativity (FRN) signal or for the event-related Theta oscillation between the adolescent non-deprived smokers and the healthy controls.
However, examination of the smoker subgroups revealed a unique and shared association between alcohol, marijuana, and tobacco and the EEG signals.
“With regard to substance use associations with the FRN smokers, regression analyses showed that cannabis use problem severity was associated with an increased FRN amplitude during the reward condition only,” Dr. Hammond said. “This finding remained significant after co-varying for demographics, for other drug use, for nicotine dependence and alcohol severity as well.
“We also found an association between alcohol problem severity and mean FRN amplitude, but with no differences across conditions,” he added. There was an association also “ between nicotine dependence and decreased FRN latency, but only during the reward and draw conditions, suggesting a nicotine severity association with speed of processing salient reward and stimuli.”
While the findings need to be better studied and replicated, “these associations may be leveraged to better personalize our interventions for these different substances of abuse,” Dr. Hammond observed. “The study also provides preliminary evidence for a dual-process model of substance use, specifically for cannabis. Cannabis severity in adolescent smokers is associated with increased bottom-up reward signaling and impaired top-down cognitive control over a salient or rewarding stimulus.”
The study was supported by the American Academy of Child and Adolescent Psychiatry and the National Institute on Drug Abuse. Dr. Hammond disclosed that he receives research funding from both organizations.
SOURCE: Hammond et al. AAAP 2017. Paper session A3.
SAN DIEGO – Among adolescent daily cigarette smokers, the individual and concomitant use of alcohol, marijuana, and tobacco have unique and common associations with reinforcement sensitivity, with negative affect, and with electrophysiological signatures of reward function, results from a novel study demonstrated.
“The co-use of alcohol, marijuana, and tobacco in youth are associated bidirectionally with higher rates of substance use, higher levels of addiction severity, and with poorer treatment outcomes for youth who present for treatment,” lead study author Christopher J. Hammond, MD, said at the annual meeting and scientific symposium of the American Academy of Addiction Psychiatry.
Currently, the effects of combined alcohol, marijuana, and tobacco use on brain function are poorly understood, noted Dr. Hammond of the division of child and adolescent psychiatry at Johns Hopkins Bayview Medical Center, Baltimore.
Published studies to date suggest that alcohol, marijuana, and tobacco use disorders are linked separately to dysfunction in the neural substrates of reward and punishment processing, but none has examined co-use or comorbid disorders in adolescents.
In a cross-sectional, single-visit study, Dr. Hammond and his associates examined a population of 36 adolescent non-deprived daily cigarette smokers and 29 healthy controls from the greater New Haven, Conn., area, matched for age, gender, and grade level. The subjects ranged in age from 14 to 20 years and were administered self-report measures characterizing tobacco, marijuana, and alcohol use. The researchers also collected urine and breathalyzer measures to characterize tobacco and cannabis use.
All subjects completed a number of self-report questionnaires characterizing their substance use patterns, their addiction severity, impulsivity, sensitivity to reward and punishment, and depression. They also underwent a 45-minute EEG, during which they completed a resting EEG test and completed a reward task.
The adolescent daily cigarette smoker group had blunted or decreased sensitivity to punishment and increased impulsivity, compared with the healthy controls, Dr. Hammond reported.
Co-occurring drug use was high in the adolescent daily smoker group, with 80% reporting heavy marijuana use (defined as using it over 100 times during adolescence), and 67% reporting heavy episodic binge drinking (defined as consuming greater than four alcoholic beverages for females during one sitting and greater than five for males at least two or more times a month).
One out of two of the daily cigarette smokers were also daily marijuana smokers, and about 75% of the adolescent smokers had a positive urine drug screen for marijuana. They smoked an average of eight cigarettes per day, used cannabis about 17 days out of the month, and they had about 1.5 binge drinking episodes per month.
Next, the researchers used linear regression analyses to examine which of the psychological variables were associated with alcohol, marijuana, and tobacco use severity within the smoker group, after co-varying for age, gender, race/ethnicity, and full-scale IQ.
“For alcohol use, we found that depression, sensitivity to reward, and impulsivity were significantly associated with alcohol problem severity scores, even after controlling for sociodemographics and other drug use (P less than .05),” Dr. Hammond said.
“For marijuana use, we found that sensitivity to reward and impulsivity were significantly associated with cannabis problem severity, even after controlling for demographics and alcohol and other drug use (P less than .01),” he continued. “For tobacco use, we found that anxiety sensitivity was significantly associated with nicotine dependence scores, even after controlling for demographics and alcohol and marijuana use (P less than .001).”
On EEG analyses, the researchers found no main effects for group or group by condition for the feedback-related negativity (FRN) signal or for the event-related Theta oscillation between the adolescent non-deprived smokers and the healthy controls.
However, examination of the smoker subgroups revealed a unique and shared association between alcohol, marijuana, and tobacco and the EEG signals.
“With regard to substance use associations with the FRN smokers, regression analyses showed that cannabis use problem severity was associated with an increased FRN amplitude during the reward condition only,” Dr. Hammond said. “This finding remained significant after co-varying for demographics, for other drug use, for nicotine dependence and alcohol severity as well.
“We also found an association between alcohol problem severity and mean FRN amplitude, but with no differences across conditions,” he added. There was an association also “ between nicotine dependence and decreased FRN latency, but only during the reward and draw conditions, suggesting a nicotine severity association with speed of processing salient reward and stimuli.”
While the findings need to be better studied and replicated, “these associations may be leveraged to better personalize our interventions for these different substances of abuse,” Dr. Hammond observed. “The study also provides preliminary evidence for a dual-process model of substance use, specifically for cannabis. Cannabis severity in adolescent smokers is associated with increased bottom-up reward signaling and impaired top-down cognitive control over a salient or rewarding stimulus.”
The study was supported by the American Academy of Child and Adolescent Psychiatry and the National Institute on Drug Abuse. Dr. Hammond disclosed that he receives research funding from both organizations.
SOURCE: Hammond et al. AAAP 2017. Paper session A3.
REPORTING FROM AAAP
Key clinical point:
Major finding: Among adolescents who smoked cigarettes daily, 80% reported co-occurring heavy marijuana use, and 67% reported heavy episodic binge drinking.
Study details: A cross-sectional, single visit study of 36 adolescent nondeprived daily cigarette smokers and 29 healthy, age-matched controls.
Disclosures: The study was supported by the American Academy of Child and Adolescent Psychiatry and the National Institute on Drug Abuse. Dr. Hammond disclosed that he receives research funding from both organizations.
Source: Hammond et al. AAAP 2017. Paper session A3.
FDA clears assay for myeloma patients
The US Food and Drug Administration (FDA) has granted 510(k) clearance for Sebia’s Hydrashift 2/4 daratumumab immunofixation assay.
This in vitro diagnostic test allows for assessment of response in patients with multiple myeloma by mitigating potential interference caused by the anti-CD38 antibody daratumumab (Darzalex®).
Daratumumab can interfere with the visualization of M-proteins in immunofixation electrophoresis.
The Hydrashift 2/4 daratumumab assay is intended to be used with Sebia’s Hydragel IF kit to provide qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis.
The assay is performed on Sebia’s Hydrasys 2 agarose gel platform.
The Hydrashift 2/4 daratumumab assay is the result of a collaboration between Sebia and Janssen Biotech, Inc. Sebia received development rights from Janssen and is the worldwide supplier of this assay.
The Hydrashift 2/4 daratumumab assay received the CE mark in November 2016. 
The US Food and Drug Administration (FDA) has granted 510(k) clearance for Sebia’s Hydrashift 2/4 daratumumab immunofixation assay.
This in vitro diagnostic test allows for assessment of response in patients with multiple myeloma by mitigating potential interference caused by the anti-CD38 antibody daratumumab (Darzalex®).
Daratumumab can interfere with the visualization of M-proteins in immunofixation electrophoresis.
The Hydrashift 2/4 daratumumab assay is intended to be used with Sebia’s Hydragel IF kit to provide qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis.
The assay is performed on Sebia’s Hydrasys 2 agarose gel platform.
The Hydrashift 2/4 daratumumab assay is the result of a collaboration between Sebia and Janssen Biotech, Inc. Sebia received development rights from Janssen and is the worldwide supplier of this assay.
The Hydrashift 2/4 daratumumab assay received the CE mark in November 2016.
The US Food and Drug Administration (FDA) has granted 510(k) clearance for Sebia’s Hydrashift 2/4 daratumumab immunofixation assay.
This in vitro diagnostic test allows for assessment of response in patients with multiple myeloma by mitigating potential interference caused by the anti-CD38 antibody daratumumab (Darzalex®).
Daratumumab can interfere with the visualization of M-proteins in immunofixation electrophoresis.
The Hydrashift 2/4 daratumumab assay is intended to be used with Sebia’s Hydragel IF kit to provide qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis.
The assay is performed on Sebia’s Hydrasys 2 agarose gel platform.
The Hydrashift 2/4 daratumumab assay is the result of a collaboration between Sebia and Janssen Biotech, Inc. Sebia received development rights from Janssen and is the worldwide supplier of this assay.
The Hydrashift 2/4 daratumumab assay received the CE mark in November 2016.
How to prioritize CVD reduction in type 2 diabetes
LOS ANGELES – In the opinion of Mikhail N. Kosiborod, MD, the paradigm of treating patients with type 2 diabetes should shift from a narrow focus on hemoglobin A1c control to a broader strategy of reducing cardiovascular risk.
“We already know that the number one killer of patients with diabetes is cardiovascular disease, and we already know that lowering HbA1c as a general strategy does not substantially lower the risk of most important CVD events,” Dr. Kosiborod, a cardiologist at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
Physicians know that some medications lower the risk of cardiovascular events – including cardiovascular death – substantially, and other drugs don’t. “The bottom line is that we are not talking about ignoring HbA1c, but it’s how you get there that’s important – how you do it and in whom,” Dr. Kosiborod explained.
He pointed to a meta-analysis of four large diabetes trials involving 27,049 participants and 2,370 major vascular events (Diabetologia. 2009 Nov;52[11]:2288-98). It found that the general strategy of targeting more-intensive glucose lowering modestly reduced nonfatal myocardial infarction and increased major hypoglycemia over 4.4 years in people with type 2 diabetes – yet there was no difference in the effect of intensive glucose control on cardiovascular death or hospitalization for heart failure.
“Some point to the benefit of glucose control on the risk of nonfatal myocardial infarction, but that’s a modest benefit,” he said. “It’s observed beyond the randomization phase of clinical trials and takes many years to see it. It’s a large, very long-term investment for a modest reduction in MI risk, with no benefit in death or heart failure. So, when you test intensive glucose control as a general strategy, it has not been successful in reducing cardiovascular complications of type 2 diabetes.”
However, there is now evidence that specific classes of medications, such as sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for glucose lowering in type 2 diabetes, can significantly reduce cardiovascular risk within a relatively short time frame.
In EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), the first trial to demonstrate such benefits, all patients had established CVD, compared with 67% of patients in CANVAS (Canagliflozin Cardiovascular Assessment Study), a second RCT program to report cardiovascular outcomes with SGLT2 inhibitors. In the meantime, about 15%-20% of patients in real-world clinical practice have established CVD.
This led Dr. Kosiborod and his associates to launch CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT2 Inhibitors), a real-world comparative effectiveness study that evaluated hospitalization for heart failure and total mortality among new users of SGLT2 inhibitors, compared with other glucose-lowering drugs.
In all, 154,528 patients in six countries were initiated on an SGLT2 inhibitor, and 154,528 were initiated on other glucose-lowering drugs (Circulation. 2017 May 18. doi: 10/1161/circulationaha.117.029190). The greatest exposure time was observed from canagliflozin (53%) followed by dapagliflozin (42%) and empagliflozin (5%).
The pooled analysis showed that initiation of SGLT2 inhibitors was associated with a significantly lower risk of heart failure events, compared with other glucose-lowering drugs (risk ratio, 0.61; P less than .001). The researchers observed an overall 39% lower risk of heart failure hospitalization, 51% reduction in total death, and 46% reduction in the composite of heart failure hospitalization or death.
“There was no heterogeneity across countries, despite the fact that the health care systems were very different and the prescribing patterns were very different,” he said.
Dr. Kosiborod, who is also professor of medicine at the University of Missouri-Kansas City, noted that 13% of patients from CVD-REAL had established CVD, while 87% did not. When comparing the results within these two key subgroups, “what’s striking is the difference in event rates, stratified by treatment allocation,” he said of the unpublished data.
“If you look at the composite outcome of heart failure or death, you see an almost seven-fold difference in annualized event rates – about 7% per year in patients with established CVD, compared with about 1% per year in the primary prevention cohort,” he explained. “But the relative risk reduction associated with SGLT2 inhibitors versus other glucose-lowering drugs is identical across both patient groups. That’s a good lesson in epidemiology: You can have patients with dramatically different absolute risks, dramatically different absolute risk reductions, and therefore dramatically different numbers needed to treat, but identical relative risk reductions.”
Dr. Kosiborod also pointed out that heart failure is emerging as one of the most important outcomes in trials patents with type 2 diabetes.
“That’s because people with diabetes who develop heart failure have very poor outcomes,” he said. “Among elderly patients with type 2 diabetes who develop new heart failure, there’s less than 25% survival at 5 years. That’s the reason, I think, that if you really want to impact survival and complication rates in people with diabetes, preventing and treating heart failure is one of the surest ways of doing so.
“You shouldn’t just think of the patient in front of you as someone who has an A1c of 7%, 8%, or 9%,” he cautioned. “You should also start thinking of where the patient is on the spectrum of cardiovascular disease, all the way from CVD risk factors only to symptomatic heart failure.”
Some evidence already exists to help clinicians make treatment decisions based on where the patients fall on that spectrum, he continued.
For example, clinical trials have demonstrated that in patients with established atherosclerotic cardiovascular disease, GLP-1 receptor agonists and SGLT2 inhibitors can reduce the risk of cardiovascular events, including, in some cases, cardiovascular death.
“We don’t have a lot of data demonstrating benefit for patients with recent acute coronary syndrome,” he said. “Some compounds have proven to be neutral, but none has been proven to save lives in this patient group.
“Now, we also have data for people with prior stroke that pioglitazone may be beneficial in managing those patients to prevent recurrent stroke and MI, based on the recent IRIS Trial, provided they don’t have heart failure at baseline,” Dr. Kosiborod added. “We don’t have definitive data yet in people with established heart failure, but those studies are ongoing.”
Dr. Kosiborod disclosed that he is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Glytec, GSK, Intarcia, Merck (Diabetes), Novartis, Novo Nordisk, Sanofi, and ZS Pharma. He has also received research grants from AstraZeneca and Boehringer Ingelheim.
LOS ANGELES – In the opinion of Mikhail N. Kosiborod, MD, the paradigm of treating patients with type 2 diabetes should shift from a narrow focus on hemoglobin A1c control to a broader strategy of reducing cardiovascular risk.
“We already know that the number one killer of patients with diabetes is cardiovascular disease, and we already know that lowering HbA1c as a general strategy does not substantially lower the risk of most important CVD events,” Dr. Kosiborod, a cardiologist at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
Physicians know that some medications lower the risk of cardiovascular events – including cardiovascular death – substantially, and other drugs don’t. “The bottom line is that we are not talking about ignoring HbA1c, but it’s how you get there that’s important – how you do it and in whom,” Dr. Kosiborod explained.
He pointed to a meta-analysis of four large diabetes trials involving 27,049 participants and 2,370 major vascular events (Diabetologia. 2009 Nov;52[11]:2288-98). It found that the general strategy of targeting more-intensive glucose lowering modestly reduced nonfatal myocardial infarction and increased major hypoglycemia over 4.4 years in people with type 2 diabetes – yet there was no difference in the effect of intensive glucose control on cardiovascular death or hospitalization for heart failure.
“Some point to the benefit of glucose control on the risk of nonfatal myocardial infarction, but that’s a modest benefit,” he said. “It’s observed beyond the randomization phase of clinical trials and takes many years to see it. It’s a large, very long-term investment for a modest reduction in MI risk, with no benefit in death or heart failure. So, when you test intensive glucose control as a general strategy, it has not been successful in reducing cardiovascular complications of type 2 diabetes.”
However, there is now evidence that specific classes of medications, such as sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for glucose lowering in type 2 diabetes, can significantly reduce cardiovascular risk within a relatively short time frame.
In EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), the first trial to demonstrate such benefits, all patients had established CVD, compared with 67% of patients in CANVAS (Canagliflozin Cardiovascular Assessment Study), a second RCT program to report cardiovascular outcomes with SGLT2 inhibitors. In the meantime, about 15%-20% of patients in real-world clinical practice have established CVD.
This led Dr. Kosiborod and his associates to launch CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT2 Inhibitors), a real-world comparative effectiveness study that evaluated hospitalization for heart failure and total mortality among new users of SGLT2 inhibitors, compared with other glucose-lowering drugs.
In all, 154,528 patients in six countries were initiated on an SGLT2 inhibitor, and 154,528 were initiated on other glucose-lowering drugs (Circulation. 2017 May 18. doi: 10/1161/circulationaha.117.029190). The greatest exposure time was observed from canagliflozin (53%) followed by dapagliflozin (42%) and empagliflozin (5%).
The pooled analysis showed that initiation of SGLT2 inhibitors was associated with a significantly lower risk of heart failure events, compared with other glucose-lowering drugs (risk ratio, 0.61; P less than .001). The researchers observed an overall 39% lower risk of heart failure hospitalization, 51% reduction in total death, and 46% reduction in the composite of heart failure hospitalization or death.
“There was no heterogeneity across countries, despite the fact that the health care systems were very different and the prescribing patterns were very different,” he said.
Dr. Kosiborod, who is also professor of medicine at the University of Missouri-Kansas City, noted that 13% of patients from CVD-REAL had established CVD, while 87% did not. When comparing the results within these two key subgroups, “what’s striking is the difference in event rates, stratified by treatment allocation,” he said of the unpublished data.
“If you look at the composite outcome of heart failure or death, you see an almost seven-fold difference in annualized event rates – about 7% per year in patients with established CVD, compared with about 1% per year in the primary prevention cohort,” he explained. “But the relative risk reduction associated with SGLT2 inhibitors versus other glucose-lowering drugs is identical across both patient groups. That’s a good lesson in epidemiology: You can have patients with dramatically different absolute risks, dramatically different absolute risk reductions, and therefore dramatically different numbers needed to treat, but identical relative risk reductions.”
Dr. Kosiborod also pointed out that heart failure is emerging as one of the most important outcomes in trials patents with type 2 diabetes.
“That’s because people with diabetes who develop heart failure have very poor outcomes,” he said. “Among elderly patients with type 2 diabetes who develop new heart failure, there’s less than 25% survival at 5 years. That’s the reason, I think, that if you really want to impact survival and complication rates in people with diabetes, preventing and treating heart failure is one of the surest ways of doing so.
“You shouldn’t just think of the patient in front of you as someone who has an A1c of 7%, 8%, or 9%,” he cautioned. “You should also start thinking of where the patient is on the spectrum of cardiovascular disease, all the way from CVD risk factors only to symptomatic heart failure.”
Some evidence already exists to help clinicians make treatment decisions based on where the patients fall on that spectrum, he continued.
For example, clinical trials have demonstrated that in patients with established atherosclerotic cardiovascular disease, GLP-1 receptor agonists and SGLT2 inhibitors can reduce the risk of cardiovascular events, including, in some cases, cardiovascular death.
“We don’t have a lot of data demonstrating benefit for patients with recent acute coronary syndrome,” he said. “Some compounds have proven to be neutral, but none has been proven to save lives in this patient group.
“Now, we also have data for people with prior stroke that pioglitazone may be beneficial in managing those patients to prevent recurrent stroke and MI, based on the recent IRIS Trial, provided they don’t have heart failure at baseline,” Dr. Kosiborod added. “We don’t have definitive data yet in people with established heart failure, but those studies are ongoing.”
Dr. Kosiborod disclosed that he is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Glytec, GSK, Intarcia, Merck (Diabetes), Novartis, Novo Nordisk, Sanofi, and ZS Pharma. He has also received research grants from AstraZeneca and Boehringer Ingelheim.
LOS ANGELES – In the opinion of Mikhail N. Kosiborod, MD, the paradigm of treating patients with type 2 diabetes should shift from a narrow focus on hemoglobin A1c control to a broader strategy of reducing cardiovascular risk.
“We already know that the number one killer of patients with diabetes is cardiovascular disease, and we already know that lowering HbA1c as a general strategy does not substantially lower the risk of most important CVD events,” Dr. Kosiborod, a cardiologist at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
Physicians know that some medications lower the risk of cardiovascular events – including cardiovascular death – substantially, and other drugs don’t. “The bottom line is that we are not talking about ignoring HbA1c, but it’s how you get there that’s important – how you do it and in whom,” Dr. Kosiborod explained.
He pointed to a meta-analysis of four large diabetes trials involving 27,049 participants and 2,370 major vascular events (Diabetologia. 2009 Nov;52[11]:2288-98). It found that the general strategy of targeting more-intensive glucose lowering modestly reduced nonfatal myocardial infarction and increased major hypoglycemia over 4.4 years in people with type 2 diabetes – yet there was no difference in the effect of intensive glucose control on cardiovascular death or hospitalization for heart failure.
“Some point to the benefit of glucose control on the risk of nonfatal myocardial infarction, but that’s a modest benefit,” he said. “It’s observed beyond the randomization phase of clinical trials and takes many years to see it. It’s a large, very long-term investment for a modest reduction in MI risk, with no benefit in death or heart failure. So, when you test intensive glucose control as a general strategy, it has not been successful in reducing cardiovascular complications of type 2 diabetes.”
However, there is now evidence that specific classes of medications, such as sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for glucose lowering in type 2 diabetes, can significantly reduce cardiovascular risk within a relatively short time frame.
In EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), the first trial to demonstrate such benefits, all patients had established CVD, compared with 67% of patients in CANVAS (Canagliflozin Cardiovascular Assessment Study), a second RCT program to report cardiovascular outcomes with SGLT2 inhibitors. In the meantime, about 15%-20% of patients in real-world clinical practice have established CVD.
This led Dr. Kosiborod and his associates to launch CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT2 Inhibitors), a real-world comparative effectiveness study that evaluated hospitalization for heart failure and total mortality among new users of SGLT2 inhibitors, compared with other glucose-lowering drugs.
In all, 154,528 patients in six countries were initiated on an SGLT2 inhibitor, and 154,528 were initiated on other glucose-lowering drugs (Circulation. 2017 May 18. doi: 10/1161/circulationaha.117.029190). The greatest exposure time was observed from canagliflozin (53%) followed by dapagliflozin (42%) and empagliflozin (5%).
The pooled analysis showed that initiation of SGLT2 inhibitors was associated with a significantly lower risk of heart failure events, compared with other glucose-lowering drugs (risk ratio, 0.61; P less than .001). The researchers observed an overall 39% lower risk of heart failure hospitalization, 51% reduction in total death, and 46% reduction in the composite of heart failure hospitalization or death.
“There was no heterogeneity across countries, despite the fact that the health care systems were very different and the prescribing patterns were very different,” he said.
Dr. Kosiborod, who is also professor of medicine at the University of Missouri-Kansas City, noted that 13% of patients from CVD-REAL had established CVD, while 87% did not. When comparing the results within these two key subgroups, “what’s striking is the difference in event rates, stratified by treatment allocation,” he said of the unpublished data.
“If you look at the composite outcome of heart failure or death, you see an almost seven-fold difference in annualized event rates – about 7% per year in patients with established CVD, compared with about 1% per year in the primary prevention cohort,” he explained. “But the relative risk reduction associated with SGLT2 inhibitors versus other glucose-lowering drugs is identical across both patient groups. That’s a good lesson in epidemiology: You can have patients with dramatically different absolute risks, dramatically different absolute risk reductions, and therefore dramatically different numbers needed to treat, but identical relative risk reductions.”
Dr. Kosiborod also pointed out that heart failure is emerging as one of the most important outcomes in trials patents with type 2 diabetes.
“That’s because people with diabetes who develop heart failure have very poor outcomes,” he said. “Among elderly patients with type 2 diabetes who develop new heart failure, there’s less than 25% survival at 5 years. That’s the reason, I think, that if you really want to impact survival and complication rates in people with diabetes, preventing and treating heart failure is one of the surest ways of doing so.
“You shouldn’t just think of the patient in front of you as someone who has an A1c of 7%, 8%, or 9%,” he cautioned. “You should also start thinking of where the patient is on the spectrum of cardiovascular disease, all the way from CVD risk factors only to symptomatic heart failure.”
Some evidence already exists to help clinicians make treatment decisions based on where the patients fall on that spectrum, he continued.
For example, clinical trials have demonstrated that in patients with established atherosclerotic cardiovascular disease, GLP-1 receptor agonists and SGLT2 inhibitors can reduce the risk of cardiovascular events, including, in some cases, cardiovascular death.
“We don’t have a lot of data demonstrating benefit for patients with recent acute coronary syndrome,” he said. “Some compounds have proven to be neutral, but none has been proven to save lives in this patient group.
“Now, we also have data for people with prior stroke that pioglitazone may be beneficial in managing those patients to prevent recurrent stroke and MI, based on the recent IRIS Trial, provided they don’t have heart failure at baseline,” Dr. Kosiborod added. “We don’t have definitive data yet in people with established heart failure, but those studies are ongoing.”
Dr. Kosiborod disclosed that he is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Glytec, GSK, Intarcia, Merck (Diabetes), Novartis, Novo Nordisk, Sanofi, and ZS Pharma. He has also received research grants from AstraZeneca and Boehringer Ingelheim.
EXPERT ANALYSIS FROM WCIRDC 2017
Heart attacks bring 12 weeks of higher stroke risk
LOS ANGELES – , based on a sample of Medicare beneficiaries.
The period of elevated stroke risk following an MI extends beyond the 30-day window that has traditionally been considered the interval of highest risk, Alexander E. Merkler, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Beyond 12 weeks after MI discharge, the stroke incidence showed no significant difference compared with people without a recent MI history, said Dr. Merkler, a neurologist at Weill Cornell Medicine in New York.
He calculated these statistically significant elevated risk rates after adjusting for demographic measures, stroke risk factors, and the comorbidities included in the Charlson Comorbidity Index.
These increased stroke rates were independent of periprocedural strokes that might have happened during MI interventions, as the analysis excluded MI patients with a history of a stroke either before or during their MI hospitalization.
To run this analysis, Dr. Merkler and his associates used data collected in a 5% sample of Medicare beneficiaries who were at least 66 years old during 2008-2015. Among these 1.7 million people were 46,182 who were hospitalized for an MI.
Several factors associated with an acute MI likely contribute to an elevated stroke risk, including stasis in the heart and generation of microthrombi, and a possibly systemic proinflammatory state, Dr. Merkler suggested.
Dr. Merkler had no disclosures.
SOURCE: Merkler AE et al., International Stroke Conference abstract 172 (Stroke. 2018 Jan; 49[Suppl 1]:A172).
LOS ANGELES – , based on a sample of Medicare beneficiaries.
The period of elevated stroke risk following an MI extends beyond the 30-day window that has traditionally been considered the interval of highest risk, Alexander E. Merkler, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Beyond 12 weeks after MI discharge, the stroke incidence showed no significant difference compared with people without a recent MI history, said Dr. Merkler, a neurologist at Weill Cornell Medicine in New York.
He calculated these statistically significant elevated risk rates after adjusting for demographic measures, stroke risk factors, and the comorbidities included in the Charlson Comorbidity Index.
These increased stroke rates were independent of periprocedural strokes that might have happened during MI interventions, as the analysis excluded MI patients with a history of a stroke either before or during their MI hospitalization.
To run this analysis, Dr. Merkler and his associates used data collected in a 5% sample of Medicare beneficiaries who were at least 66 years old during 2008-2015. Among these 1.7 million people were 46,182 who were hospitalized for an MI.
Several factors associated with an acute MI likely contribute to an elevated stroke risk, including stasis in the heart and generation of microthrombi, and a possibly systemic proinflammatory state, Dr. Merkler suggested.
Dr. Merkler had no disclosures.
SOURCE: Merkler AE et al., International Stroke Conference abstract 172 (Stroke. 2018 Jan; 49[Suppl 1]:A172).
LOS ANGELES – , based on a sample of Medicare beneficiaries.
The period of elevated stroke risk following an MI extends beyond the 30-day window that has traditionally been considered the interval of highest risk, Alexander E. Merkler, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Beyond 12 weeks after MI discharge, the stroke incidence showed no significant difference compared with people without a recent MI history, said Dr. Merkler, a neurologist at Weill Cornell Medicine in New York.
He calculated these statistically significant elevated risk rates after adjusting for demographic measures, stroke risk factors, and the comorbidities included in the Charlson Comorbidity Index.
These increased stroke rates were independent of periprocedural strokes that might have happened during MI interventions, as the analysis excluded MI patients with a history of a stroke either before or during their MI hospitalization.
To run this analysis, Dr. Merkler and his associates used data collected in a 5% sample of Medicare beneficiaries who were at least 66 years old during 2008-2015. Among these 1.7 million people were 46,182 who were hospitalized for an MI.
Several factors associated with an acute MI likely contribute to an elevated stroke risk, including stasis in the heart and generation of microthrombi, and a possibly systemic proinflammatory state, Dr. Merkler suggested.
Dr. Merkler had no disclosures.
SOURCE: Merkler AE et al., International Stroke Conference abstract 172 (Stroke. 2018 Jan; 49[Suppl 1]:A172).
REPORTING FROM ISC 2018
Key clinical point: A patient’s stroke risk is elevated for 12 weeks following a myocardial infarction.
Major finding: The stroke rate was 2.7-fold, 2.0-fold, and 1.6-fold above background at 4, 8, and 12 weeks after an MI.
Study details: A review of 1.7 million Medicare beneficiaries during 2008-2015.
Disclosures: Dr. Merkler had no disclosures.
Source: Merkler AE et al., International Stroke Conference abstract 172 (Stroke. 2018 Jan;49[Suppl 1]:A172).
Pembrolizumab plus SBRT shows promise for advanced solid tumors
SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.
Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.
When responses in the non-irradiated lesions (out-of-field responses) were measured based on a 30% reduction in any single lesion, the rate was 26.9%. But when defined by a 30% reduction in aggregate diameter of the non-irradiated measurable lesions, the rate was 13.5%, he said. While both approaches for measuring response are acceptable, Dr. Lemons noted, it’s important to be sure which one is being used in a given study.
Overall, 73 patients received both SBRT and pembrolizumab (5 had no imaging follow-up). They had a mean age of 62 years and a median of five prior therapies. Cancer types included ovarian/fallopian tube cancer (12.3%), non–small cell lung cancer (9.6%), breast cancer (8.2%), cholangiocarcinoma (8.2%), endometrial cancer (8.2%), colorectal cancer (6.8%), head and neck cancer (5.5%), and other tumors, each with less than 5% accrual (41.2%).
The number of sites treated with SBRT was two in 94.5% of patients, three in 4.1%, and four in 1.3%; 151 lesions in total were treated.
The premise for combining pembrolizumab and SBRT is that response to anti-programmed cell death-1 (PD1) therapy seems to correspond with interferon-gamma signaling, and that SBRT can stimulate innate and adaptive immunity to potentially augment immunotherapy, Dr. Lemons explained. In addition, anti-PD1 treatment outcomes are improved with lower disease burden.
Multi-site radiation is an emerging paradigm for eradicating metastatic disease, he said.
Patients included in the study had metastatic solid tumors and had progressed on standard treatment. They had measurable disease by RECIST, and metastases amenable to SBRT with 0.25 cc to 65 cc of viable tumor.
Tumors larger than 65 cc were partially targeted with radiotherapy. Radiation doses were adapted from recently completed and ongoing National Cancer Institute trials and ranged from 30-50 Gy (3-5 fractions) based on anatomic location.
Pembrolizumab was initiated within 7 days of the final SBRT treatment.
Dose-limiting toxicities, all grade 3, occurred in six patients during a median follow-up of 5.5 months, and included pneumonitis in three patients, hepatic failure in one patient, and colitis in two patients, but there were no radiation dose reductions, Dr. Lemons said.
“This is the first and largest prospective trial to determine the safety of this combination,” he explained. “There was some intriguing clinical activity ... and we feel that this justifies further randomized studies
The University of Chicago sponsored the study. Dr. Lemons reported having no disclosures.
SOURCE: Lemons J et al., ASCO-SITC abstract #20.
SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.
Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.
When responses in the non-irradiated lesions (out-of-field responses) were measured based on a 30% reduction in any single lesion, the rate was 26.9%. But when defined by a 30% reduction in aggregate diameter of the non-irradiated measurable lesions, the rate was 13.5%, he said. While both approaches for measuring response are acceptable, Dr. Lemons noted, it’s important to be sure which one is being used in a given study.
Overall, 73 patients received both SBRT and pembrolizumab (5 had no imaging follow-up). They had a mean age of 62 years and a median of five prior therapies. Cancer types included ovarian/fallopian tube cancer (12.3%), non–small cell lung cancer (9.6%), breast cancer (8.2%), cholangiocarcinoma (8.2%), endometrial cancer (8.2%), colorectal cancer (6.8%), head and neck cancer (5.5%), and other tumors, each with less than 5% accrual (41.2%).
The number of sites treated with SBRT was two in 94.5% of patients, three in 4.1%, and four in 1.3%; 151 lesions in total were treated.
The premise for combining pembrolizumab and SBRT is that response to anti-programmed cell death-1 (PD1) therapy seems to correspond with interferon-gamma signaling, and that SBRT can stimulate innate and adaptive immunity to potentially augment immunotherapy, Dr. Lemons explained. In addition, anti-PD1 treatment outcomes are improved with lower disease burden.
Multi-site radiation is an emerging paradigm for eradicating metastatic disease, he said.
Patients included in the study had metastatic solid tumors and had progressed on standard treatment. They had measurable disease by RECIST, and metastases amenable to SBRT with 0.25 cc to 65 cc of viable tumor.
Tumors larger than 65 cc were partially targeted with radiotherapy. Radiation doses were adapted from recently completed and ongoing National Cancer Institute trials and ranged from 30-50 Gy (3-5 fractions) based on anatomic location.
Pembrolizumab was initiated within 7 days of the final SBRT treatment.
Dose-limiting toxicities, all grade 3, occurred in six patients during a median follow-up of 5.5 months, and included pneumonitis in three patients, hepatic failure in one patient, and colitis in two patients, but there were no radiation dose reductions, Dr. Lemons said.
“This is the first and largest prospective trial to determine the safety of this combination,” he explained. “There was some intriguing clinical activity ... and we feel that this justifies further randomized studies
The University of Chicago sponsored the study. Dr. Lemons reported having no disclosures.
SOURCE: Lemons J et al., ASCO-SITC abstract #20.
SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.
Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.
When responses in the non-irradiated lesions (out-of-field responses) were measured based on a 30% reduction in any single lesion, the rate was 26.9%. But when defined by a 30% reduction in aggregate diameter of the non-irradiated measurable lesions, the rate was 13.5%, he said. While both approaches for measuring response are acceptable, Dr. Lemons noted, it’s important to be sure which one is being used in a given study.
Overall, 73 patients received both SBRT and pembrolizumab (5 had no imaging follow-up). They had a mean age of 62 years and a median of five prior therapies. Cancer types included ovarian/fallopian tube cancer (12.3%), non–small cell lung cancer (9.6%), breast cancer (8.2%), cholangiocarcinoma (8.2%), endometrial cancer (8.2%), colorectal cancer (6.8%), head and neck cancer (5.5%), and other tumors, each with less than 5% accrual (41.2%).
The number of sites treated with SBRT was two in 94.5% of patients, three in 4.1%, and four in 1.3%; 151 lesions in total were treated.
The premise for combining pembrolizumab and SBRT is that response to anti-programmed cell death-1 (PD1) therapy seems to correspond with interferon-gamma signaling, and that SBRT can stimulate innate and adaptive immunity to potentially augment immunotherapy, Dr. Lemons explained. In addition, anti-PD1 treatment outcomes are improved with lower disease burden.
Multi-site radiation is an emerging paradigm for eradicating metastatic disease, he said.
Patients included in the study had metastatic solid tumors and had progressed on standard treatment. They had measurable disease by RECIST, and metastases amenable to SBRT with 0.25 cc to 65 cc of viable tumor.
Tumors larger than 65 cc were partially targeted with radiotherapy. Radiation doses were adapted from recently completed and ongoing National Cancer Institute trials and ranged from 30-50 Gy (3-5 fractions) based on anatomic location.
Pembrolizumab was initiated within 7 days of the final SBRT treatment.
Dose-limiting toxicities, all grade 3, occurred in six patients during a median follow-up of 5.5 months, and included pneumonitis in three patients, hepatic failure in one patient, and colitis in two patients, but there were no radiation dose reductions, Dr. Lemons said.
“This is the first and largest prospective trial to determine the safety of this combination,” he explained. “There was some intriguing clinical activity ... and we feel that this justifies further randomized studies
The University of Chicago sponsored the study. Dr. Lemons reported having no disclosures.
SOURCE: Lemons J et al., ASCO-SITC abstract #20.
REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM
Key clinical point: Pembrolizumab plus multi-site SBRT appears safe and effective for advanced solid tumors.
Major finding: The overall objective response rate was 13.2%.
Study details: A phase 1 study of 79 patients.
Disclosures: The University of Chicago sponsored the study. Dr. Lemons reported having no disclosures
Source: Lemons J et al. ASCO-SITC abstract #20.
Trial seeks improved regimens for pregnant women with HIV
A new phase 3 trial will compare the safety and efficacy of the current first-line antiretroviral regimen for pregnant women with HIV to that of two other regimens, each of which include the newer antiretroviral drug dolutegravir (DTG).
The World Health Organization recommends efavirenz /emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) for pregnant women who have HIV and live in low-resource settings, but the regimen is not well tolerated.
The new phase 3 trial, known as IMPAACT 2010 or VESTED (Virologic Efficacy and Safety of Antiretroviral Therapy Combinations with TAF/TDF, EFV, and DTG), will compare the recommended regimen with DTG plus emtricitabine/tenofovir alafenamide (FTC/TAF) and DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in hopes of finding a better alternative.
The trial has sites open in Zimbabwe and the United States, but more sites are expected to open over the coming months in Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand, Uganda, the United States, and Zimbabwe, according to a statement from the U.S. National Institutes of Health.
The study is receiving funding in part from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as from the National Institute of Allergy and Infectious Diseases. The drugs used in the study have been provided by Gilead Sciences, Mylan, and ViiV Healthcare. ViiV is also covering nonparticipant costs for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network, which is conducting the study.
A new phase 3 trial will compare the safety and efficacy of the current first-line antiretroviral regimen for pregnant women with HIV to that of two other regimens, each of which include the newer antiretroviral drug dolutegravir (DTG).
The World Health Organization recommends efavirenz /emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) for pregnant women who have HIV and live in low-resource settings, but the regimen is not well tolerated.
The new phase 3 trial, known as IMPAACT 2010 or VESTED (Virologic Efficacy and Safety of Antiretroviral Therapy Combinations with TAF/TDF, EFV, and DTG), will compare the recommended regimen with DTG plus emtricitabine/tenofovir alafenamide (FTC/TAF) and DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in hopes of finding a better alternative.
The trial has sites open in Zimbabwe and the United States, but more sites are expected to open over the coming months in Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand, Uganda, the United States, and Zimbabwe, according to a statement from the U.S. National Institutes of Health.
The study is receiving funding in part from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as from the National Institute of Allergy and Infectious Diseases. The drugs used in the study have been provided by Gilead Sciences, Mylan, and ViiV Healthcare. ViiV is also covering nonparticipant costs for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network, which is conducting the study.
A new phase 3 trial will compare the safety and efficacy of the current first-line antiretroviral regimen for pregnant women with HIV to that of two other regimens, each of which include the newer antiretroviral drug dolutegravir (DTG).
The World Health Organization recommends efavirenz /emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) for pregnant women who have HIV and live in low-resource settings, but the regimen is not well tolerated.
The new phase 3 trial, known as IMPAACT 2010 or VESTED (Virologic Efficacy and Safety of Antiretroviral Therapy Combinations with TAF/TDF, EFV, and DTG), will compare the recommended regimen with DTG plus emtricitabine/tenofovir alafenamide (FTC/TAF) and DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in hopes of finding a better alternative.
The trial has sites open in Zimbabwe and the United States, but more sites are expected to open over the coming months in Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand, Uganda, the United States, and Zimbabwe, according to a statement from the U.S. National Institutes of Health.
The study is receiving funding in part from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as from the National Institute of Allergy and Infectious Diseases. The drugs used in the study have been provided by Gilead Sciences, Mylan, and ViiV Healthcare. ViiV is also covering nonparticipant costs for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network, which is conducting the study.