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Prolonged DAPT doesn’t help left main CAD
SAN DIEGO – Among patients who receive a drug-eluting stent (DES) in their left main coronary artery (LMCA), continuation of dual antiplatelet therapy (DAPT) past 1 year appears to provide no benefit.
The results come from a subanalysis of the EXCEL trial, which compared the Xience DES to coronary artery bypass graft (CABG) surgery in LMCA lesions.
The LMCA is worrisome to a lot of physicians because of the large amount of myocardial tissue it contains, and they often prescribe DAPT past the generally recommended 1 year. “It’s this magic thing, that ‘Well, it’s left main stenting, and you’d better protect the patient.’ But it turns out that it doesn’t,” said Sorin Brener, MD, director of the catheterization lab at New York Methodist Hospital, who presented the results of the study at the Transcatheter Cardiovascular Therapeutics annual meeting.
The researchers compared patients in both groups who opted to stop DAPT after 1 year versus those who continued therapy out to 3 years, and the news was not favorable for continuation. A composite of death, myocardial infarction, or stroke was higher among patients who continued DAPT, though the results did not reach statistical significance.
It’s possible that patients who continued DAPT were more ill on average. “Obviously, there could be cases where the doctor decided they deserved more prolonged therapy, but it’s not measurable, so I don’t think they were sicker,” said Dr. Brener.
The study was also underpowered. Those worse trends probably don’t represent a real signal, according to Dr. Brener. Rather, they suggest that there is no significant difference between the approaches. “The signal just tells you that there is no difference, and that prolonging DAPT probably just induces some minor bleeding, but it doesn’t protect you. So the message would be that you should treat all your patients the same way regardless of where you put the stent,” said Dr. Brener.
The researchers compared data from 497 patients in the EXCEL trial who continued DAPT out to 3 years with that from 136 who stopped DAPT early (115 stopped in year 1-2; 21 stopped in year 2-3). The baseline characteristics of the two groups were similar except for a higher incidence of recent MI in the group that stopped DAPT early (21.3% vs. 13.7%; P = .03).
At 3 years, death, MI, or stroke occurred in 7.8% of the continuation group and in 5.2% of the patients who stopped DAPT. All-cause mortality was 5.8% in the continuation group compared with 2.3% of those who stopped. When the researchers restricted the analysis to patients who presented with acute coronary syndrome, 7.6% and 3.6%, respectively, met the primary endpoint. None of these differences reached statistical significance.
The study was limited by a high dropout rate from DAPT in the first year: 152 patients stopped taking the medication even though they experienced no events, and they were excluded from the analysis.
The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
SOURCE: Brener S. TCT 2018, Abstract TCT-1.
SAN DIEGO – Among patients who receive a drug-eluting stent (DES) in their left main coronary artery (LMCA), continuation of dual antiplatelet therapy (DAPT) past 1 year appears to provide no benefit.
The results come from a subanalysis of the EXCEL trial, which compared the Xience DES to coronary artery bypass graft (CABG) surgery in LMCA lesions.
The LMCA is worrisome to a lot of physicians because of the large amount of myocardial tissue it contains, and they often prescribe DAPT past the generally recommended 1 year. “It’s this magic thing, that ‘Well, it’s left main stenting, and you’d better protect the patient.’ But it turns out that it doesn’t,” said Sorin Brener, MD, director of the catheterization lab at New York Methodist Hospital, who presented the results of the study at the Transcatheter Cardiovascular Therapeutics annual meeting.
The researchers compared patients in both groups who opted to stop DAPT after 1 year versus those who continued therapy out to 3 years, and the news was not favorable for continuation. A composite of death, myocardial infarction, or stroke was higher among patients who continued DAPT, though the results did not reach statistical significance.
It’s possible that patients who continued DAPT were more ill on average. “Obviously, there could be cases where the doctor decided they deserved more prolonged therapy, but it’s not measurable, so I don’t think they were sicker,” said Dr. Brener.
The study was also underpowered. Those worse trends probably don’t represent a real signal, according to Dr. Brener. Rather, they suggest that there is no significant difference between the approaches. “The signal just tells you that there is no difference, and that prolonging DAPT probably just induces some minor bleeding, but it doesn’t protect you. So the message would be that you should treat all your patients the same way regardless of where you put the stent,” said Dr. Brener.
The researchers compared data from 497 patients in the EXCEL trial who continued DAPT out to 3 years with that from 136 who stopped DAPT early (115 stopped in year 1-2; 21 stopped in year 2-3). The baseline characteristics of the two groups were similar except for a higher incidence of recent MI in the group that stopped DAPT early (21.3% vs. 13.7%; P = .03).
At 3 years, death, MI, or stroke occurred in 7.8% of the continuation group and in 5.2% of the patients who stopped DAPT. All-cause mortality was 5.8% in the continuation group compared with 2.3% of those who stopped. When the researchers restricted the analysis to patients who presented with acute coronary syndrome, 7.6% and 3.6%, respectively, met the primary endpoint. None of these differences reached statistical significance.
The study was limited by a high dropout rate from DAPT in the first year: 152 patients stopped taking the medication even though they experienced no events, and they were excluded from the analysis.
The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
SOURCE: Brener S. TCT 2018, Abstract TCT-1.
SAN DIEGO – Among patients who receive a drug-eluting stent (DES) in their left main coronary artery (LMCA), continuation of dual antiplatelet therapy (DAPT) past 1 year appears to provide no benefit.
The results come from a subanalysis of the EXCEL trial, which compared the Xience DES to coronary artery bypass graft (CABG) surgery in LMCA lesions.
The LMCA is worrisome to a lot of physicians because of the large amount of myocardial tissue it contains, and they often prescribe DAPT past the generally recommended 1 year. “It’s this magic thing, that ‘Well, it’s left main stenting, and you’d better protect the patient.’ But it turns out that it doesn’t,” said Sorin Brener, MD, director of the catheterization lab at New York Methodist Hospital, who presented the results of the study at the Transcatheter Cardiovascular Therapeutics annual meeting.
The researchers compared patients in both groups who opted to stop DAPT after 1 year versus those who continued therapy out to 3 years, and the news was not favorable for continuation. A composite of death, myocardial infarction, or stroke was higher among patients who continued DAPT, though the results did not reach statistical significance.
It’s possible that patients who continued DAPT were more ill on average. “Obviously, there could be cases where the doctor decided they deserved more prolonged therapy, but it’s not measurable, so I don’t think they were sicker,” said Dr. Brener.
The study was also underpowered. Those worse trends probably don’t represent a real signal, according to Dr. Brener. Rather, they suggest that there is no significant difference between the approaches. “The signal just tells you that there is no difference, and that prolonging DAPT probably just induces some minor bleeding, but it doesn’t protect you. So the message would be that you should treat all your patients the same way regardless of where you put the stent,” said Dr. Brener.
The researchers compared data from 497 patients in the EXCEL trial who continued DAPT out to 3 years with that from 136 who stopped DAPT early (115 stopped in year 1-2; 21 stopped in year 2-3). The baseline characteristics of the two groups were similar except for a higher incidence of recent MI in the group that stopped DAPT early (21.3% vs. 13.7%; P = .03).
At 3 years, death, MI, or stroke occurred in 7.8% of the continuation group and in 5.2% of the patients who stopped DAPT. All-cause mortality was 5.8% in the continuation group compared with 2.3% of those who stopped. When the researchers restricted the analysis to patients who presented with acute coronary syndrome, 7.6% and 3.6%, respectively, met the primary endpoint. None of these differences reached statistical significance.
The study was limited by a high dropout rate from DAPT in the first year: 152 patients stopped taking the medication even though they experienced no events, and they were excluded from the analysis.
The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
SOURCE: Brener S. TCT 2018, Abstract TCT-1.
REPORTING FROM TCT 2018
Key clinical point: Prolonged DAPT was not associated with better outcomes.
Major finding: Composite death, myocardial infarction, and stroke was similar between the two groups.
Study details: A post hoc analysis of 633 patients in the EXCEL trial.
Disclosures: The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
Source: Brener S. TCT 2018, Abstract TCT-1.
Experts advise risk stratification for newborn early-onset sepsis
according to a pair of clinical reports published in Pediatrics.
Early-onset sepsis usually begins during labor in term infants, but in preterm infants, “the pathogenesis of preterm EOS likely begins before the onset of labor in many cases of preterm labor and/or PROM [premature rupture of membranes],” wrote Karen M. Puopolo, MD, of the University of Pennsylvania, Philadelphia, and her colleagues.
In the report on preterm infants, the researchers noted that EOS risk assessment using gestational age can be useful for term infants, but not for preterm infants. Instead, they advised categorizing preterm infants as low risk based on birth circumstances. Low-risk preterm infants were defined as those born by cesarean delivery because of maternal noninfectious illness or placental insufficiency in the absence of labor, attempts to induce labor, or rupture of membranes before delivery. Consider the risk/benefit balance of performing an EOS laboratory evaluation and empirical antibiotics, depending on the neonate’s clinical condition, the researchers said.
Preterm infants at high risk for EOS are those born preterm because of maternal cervical incompetence, preterm labor, premature rupture of membranes, clinical concerns for intra-amniotic infection, or acute onset of “unexplained nonreassuring fetal status,” Dr. Puopolo and her associates said. These infants should be managed with a blood culture and empirical antibiotics.
“The combination of ampicillin and gentamicin is the most appropriate empirical antibiotic regimen for infants at risk for EOS,” they noted. “Empirical administration of additional broad-spectrum antibiotics may be indicated in preterm infants who are severely ill and at a high risk for EOS, particularly after prolonged antepartum maternal antibiotic treatment,” they said. Antibiotics should be discontinued by 36-48 hours of incubation unless the infant shows signs of site-specific infection.
In the second report, again with Dr. Puopolo as the primary author, management of EOS was addressed for full-term infants, defined as those born at 35 weeks’ gestation or later.
Infants born at 35 weeks’ gestation or later can be stratified for EOS risk based on algorithms for intrapartum risk factors as well as risk assessments based on these risk factors and infant examinations, the researchers said.
There are a variety of acceptable approaches to risk stratification: categorical algorithms with threshold values for intrapartum risk factors; multivariate risk assessment based on both intrapartum risk factors (such as maternal chorioamnionitis, group B streptococcus colonization, adequacy of intrapartum antibiotic prophylaxis, and duration of ROM); and serial infant examination to detect clinical signs of illness after birth, Dr. Puopolo and her associates wrote.
They recommended that birth centers choose which type of EOS risk assessment to use and tailor it to their own situation. Once local guidelines are developed, ongoing surveillance is suggested.
The same recommendations apply to term infants as preterm infants regarding first-choice use of ampicillin and gentamicin when necessary, to be discontinued when blood cultures are sterile at 36-48 hours of incubation in the absence of site-specific infection, they said.
The reports do “not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate,” Dr. Puopolo and her associates noted.
The researchers had no financial conflicts to disclose, and there was no external funding.
SOURCE: Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2896; Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2894.
according to a pair of clinical reports published in Pediatrics.
Early-onset sepsis usually begins during labor in term infants, but in preterm infants, “the pathogenesis of preterm EOS likely begins before the onset of labor in many cases of preterm labor and/or PROM [premature rupture of membranes],” wrote Karen M. Puopolo, MD, of the University of Pennsylvania, Philadelphia, and her colleagues.
In the report on preterm infants, the researchers noted that EOS risk assessment using gestational age can be useful for term infants, but not for preterm infants. Instead, they advised categorizing preterm infants as low risk based on birth circumstances. Low-risk preterm infants were defined as those born by cesarean delivery because of maternal noninfectious illness or placental insufficiency in the absence of labor, attempts to induce labor, or rupture of membranes before delivery. Consider the risk/benefit balance of performing an EOS laboratory evaluation and empirical antibiotics, depending on the neonate’s clinical condition, the researchers said.
Preterm infants at high risk for EOS are those born preterm because of maternal cervical incompetence, preterm labor, premature rupture of membranes, clinical concerns for intra-amniotic infection, or acute onset of “unexplained nonreassuring fetal status,” Dr. Puopolo and her associates said. These infants should be managed with a blood culture and empirical antibiotics.
“The combination of ampicillin and gentamicin is the most appropriate empirical antibiotic regimen for infants at risk for EOS,” they noted. “Empirical administration of additional broad-spectrum antibiotics may be indicated in preterm infants who are severely ill and at a high risk for EOS, particularly after prolonged antepartum maternal antibiotic treatment,” they said. Antibiotics should be discontinued by 36-48 hours of incubation unless the infant shows signs of site-specific infection.
In the second report, again with Dr. Puopolo as the primary author, management of EOS was addressed for full-term infants, defined as those born at 35 weeks’ gestation or later.
Infants born at 35 weeks’ gestation or later can be stratified for EOS risk based on algorithms for intrapartum risk factors as well as risk assessments based on these risk factors and infant examinations, the researchers said.
There are a variety of acceptable approaches to risk stratification: categorical algorithms with threshold values for intrapartum risk factors; multivariate risk assessment based on both intrapartum risk factors (such as maternal chorioamnionitis, group B streptococcus colonization, adequacy of intrapartum antibiotic prophylaxis, and duration of ROM); and serial infant examination to detect clinical signs of illness after birth, Dr. Puopolo and her associates wrote.
They recommended that birth centers choose which type of EOS risk assessment to use and tailor it to their own situation. Once local guidelines are developed, ongoing surveillance is suggested.
The same recommendations apply to term infants as preterm infants regarding first-choice use of ampicillin and gentamicin when necessary, to be discontinued when blood cultures are sterile at 36-48 hours of incubation in the absence of site-specific infection, they said.
The reports do “not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate,” Dr. Puopolo and her associates noted.
The researchers had no financial conflicts to disclose, and there was no external funding.
SOURCE: Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2896; Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2894.
according to a pair of clinical reports published in Pediatrics.
Early-onset sepsis usually begins during labor in term infants, but in preterm infants, “the pathogenesis of preterm EOS likely begins before the onset of labor in many cases of preterm labor and/or PROM [premature rupture of membranes],” wrote Karen M. Puopolo, MD, of the University of Pennsylvania, Philadelphia, and her colleagues.
In the report on preterm infants, the researchers noted that EOS risk assessment using gestational age can be useful for term infants, but not for preterm infants. Instead, they advised categorizing preterm infants as low risk based on birth circumstances. Low-risk preterm infants were defined as those born by cesarean delivery because of maternal noninfectious illness or placental insufficiency in the absence of labor, attempts to induce labor, or rupture of membranes before delivery. Consider the risk/benefit balance of performing an EOS laboratory evaluation and empirical antibiotics, depending on the neonate’s clinical condition, the researchers said.
Preterm infants at high risk for EOS are those born preterm because of maternal cervical incompetence, preterm labor, premature rupture of membranes, clinical concerns for intra-amniotic infection, or acute onset of “unexplained nonreassuring fetal status,” Dr. Puopolo and her associates said. These infants should be managed with a blood culture and empirical antibiotics.
“The combination of ampicillin and gentamicin is the most appropriate empirical antibiotic regimen for infants at risk for EOS,” they noted. “Empirical administration of additional broad-spectrum antibiotics may be indicated in preterm infants who are severely ill and at a high risk for EOS, particularly after prolonged antepartum maternal antibiotic treatment,” they said. Antibiotics should be discontinued by 36-48 hours of incubation unless the infant shows signs of site-specific infection.
In the second report, again with Dr. Puopolo as the primary author, management of EOS was addressed for full-term infants, defined as those born at 35 weeks’ gestation or later.
Infants born at 35 weeks’ gestation or later can be stratified for EOS risk based on algorithms for intrapartum risk factors as well as risk assessments based on these risk factors and infant examinations, the researchers said.
There are a variety of acceptable approaches to risk stratification: categorical algorithms with threshold values for intrapartum risk factors; multivariate risk assessment based on both intrapartum risk factors (such as maternal chorioamnionitis, group B streptococcus colonization, adequacy of intrapartum antibiotic prophylaxis, and duration of ROM); and serial infant examination to detect clinical signs of illness after birth, Dr. Puopolo and her associates wrote.
They recommended that birth centers choose which type of EOS risk assessment to use and tailor it to their own situation. Once local guidelines are developed, ongoing surveillance is suggested.
The same recommendations apply to term infants as preterm infants regarding first-choice use of ampicillin and gentamicin when necessary, to be discontinued when blood cultures are sterile at 36-48 hours of incubation in the absence of site-specific infection, they said.
The reports do “not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate,” Dr. Puopolo and her associates noted.
The researchers had no financial conflicts to disclose, and there was no external funding.
SOURCE: Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2896; Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2894.
FROM PEDIATRICS
Dementia linked to increased mortality risk in adults with Down syndrome
Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia, according to results of a recent prospective study.
More than 70% of the individuals with Down syndrome who died over the course of follow-up had a clinical diagnosis of dementia in this longitudinal study of community dwelling participants, many of whom had factors associated with dementia such as the apolipoprotein E (APOE) genotype.
The findings of this study support an “urgent need” for clinical trials of treatment that might delay or prevent dementia in individuals with Down syndrome, said the investigators, led by Rosalyn Hithersay, MSc, of the department of forensic and neurodevelopmental sciences in the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London (United Kingdom).
“We hope that our findings can improve clinical care by identifying factors associated with increased risk for dementia and mortality risk in this population, suggesting the potentially beneficial effects of existing medication options and helping clinicians provide prognostic information for their patients,” the authors wrote in JAMA Neurology.
The risk of dementia in individuals with Down syndrome has grown to “exceptional” levels, alongside a dramatic increase in life expectancy in these patients, from just 10 years of age some 50 years ago, to nearly 64 years today, investigators said.
Although other research has confirmed that dementia is frequently recorded as a contributory factor in Down syndrome deaths in recent years, this latest study provides crude mortality rates and exploratory analyses of factors that may modify mortality and dementia risk, according to the researchers.
Their study included 211 individuals with Down syndrome who were aged at least 36 years at study entry and followed for a total of 503.92 person-years, the investigators reported.
A total of 27 individuals died during follow-up, with a median age at death of 57 years; of those individuals, 19 (70.37%) had a clinical diagnosis of dementia, according to the report.
The crude mortality rate for individuals with dementia was nearly 1,192 deaths per 10,000 person-years, compared with 232 deaths per 10,000 person-years for those with no dementia diagnosis, the investigators found.
Further analysis showed that factors independently associated with mortality in those with a dementia diagnosis included APOE genotype, dementia medication status, early-onset epilepsy, and presence of two or more comorbid conditions.
In a combined model, APOE genotype was significantly associated with mortality risk, they added.
Among the eight individuals with Down syndrome who died without a dementia diagnosis, one reportedly had early signs of cognitive decline, and two had late-onset epilepsy.
Late-onset epilepsy, identified in seven individuals (4.8%) with no dementia diagnosis in this study, was the only factor associated with mortality in individuals without dementia, conferring a 10-fold increase in risk of that outcome, according to the analysis.
“This raises the question of whether seizures can begin in the absence of other features of dementia in individuals with Down syndrome or whether these seven individuals had significant AD pathology and neurological symptoms but had yet to receive a formal dementia diagnosis,” the researchers wrote in a discussion of results.
The authors reported no conflict of interest disclosures related to the study. Their research was supported by UK National Institute for Health Research networks and participating National Health Services trusts, as well as a Wellcome Trust Strategic Award to the London Down Syndrome Consortium.
SOURCE: Hithersay R et al. JAMA Neurol. 2018 Nov 19. doi: 10.1001/jamaneurol.2018.3616
Although this prospective longitudinal study has a limited sample size and short follow-up, the finding that dementia is the proximate cause of death in approximately 70% of individuals with Down syndrome was “astonishing,” Michael S. Rafii, MD, PhD, and Stephanie L. Santoro, MD, wrote in an editorial.
Mortality rates among individuals with Down syndrome were five times higher in those with dementia as compared with those without dementia in this study, with a median age at death of 57 years (see article).
“By comparison, in the general population, dementia of any subtype is listed in only 18% of death certificates for those older than 65 years, with mortality rates being slightly less than twofold higher in those with dementia than those without,” Dr. Rafiii and Dr. Santoro wrote in their editorial.
Results of the study imply that most older individuals with Down syndrome will have dementia at the time of death, which suggests that these individuals and their families have a “greater need” to plan for a life stage that includes dementia, the authors said.
Physicians and health care systems could consider screening for dementia and epilepsy as part of their standard care practices for older adults with Down syndrome based on these study results, they added.
“Although consensus guidelines and screening tools have been published for the evaluation and management of dementia in Down syndrome, it remains unclear if there has been widespread implementation of these,” the authors said.
Dr. Rafii is with the Alzheimer’s Therapeutic Research Institute at the University of Southern California, San Diego. Coauthor Dr. Santoro is with the Down Syndrome Program at Massachusetts General Hospital and with Harvard Medical School, both in Boston. The authors reported no conflict of interest disclosures related to their editorial, which appears in JAMA Neurology .
Although this prospective longitudinal study has a limited sample size and short follow-up, the finding that dementia is the proximate cause of death in approximately 70% of individuals with Down syndrome was “astonishing,” Michael S. Rafii, MD, PhD, and Stephanie L. Santoro, MD, wrote in an editorial.
Mortality rates among individuals with Down syndrome were five times higher in those with dementia as compared with those without dementia in this study, with a median age at death of 57 years (see article).
“By comparison, in the general population, dementia of any subtype is listed in only 18% of death certificates for those older than 65 years, with mortality rates being slightly less than twofold higher in those with dementia than those without,” Dr. Rafiii and Dr. Santoro wrote in their editorial.
Results of the study imply that most older individuals with Down syndrome will have dementia at the time of death, which suggests that these individuals and their families have a “greater need” to plan for a life stage that includes dementia, the authors said.
Physicians and health care systems could consider screening for dementia and epilepsy as part of their standard care practices for older adults with Down syndrome based on these study results, they added.
“Although consensus guidelines and screening tools have been published for the evaluation and management of dementia in Down syndrome, it remains unclear if there has been widespread implementation of these,” the authors said.
Dr. Rafii is with the Alzheimer’s Therapeutic Research Institute at the University of Southern California, San Diego. Coauthor Dr. Santoro is with the Down Syndrome Program at Massachusetts General Hospital and with Harvard Medical School, both in Boston. The authors reported no conflict of interest disclosures related to their editorial, which appears in JAMA Neurology .
Although this prospective longitudinal study has a limited sample size and short follow-up, the finding that dementia is the proximate cause of death in approximately 70% of individuals with Down syndrome was “astonishing,” Michael S. Rafii, MD, PhD, and Stephanie L. Santoro, MD, wrote in an editorial.
Mortality rates among individuals with Down syndrome were five times higher in those with dementia as compared with those without dementia in this study, with a median age at death of 57 years (see article).
“By comparison, in the general population, dementia of any subtype is listed in only 18% of death certificates for those older than 65 years, with mortality rates being slightly less than twofold higher in those with dementia than those without,” Dr. Rafiii and Dr. Santoro wrote in their editorial.
Results of the study imply that most older individuals with Down syndrome will have dementia at the time of death, which suggests that these individuals and their families have a “greater need” to plan for a life stage that includes dementia, the authors said.
Physicians and health care systems could consider screening for dementia and epilepsy as part of their standard care practices for older adults with Down syndrome based on these study results, they added.
“Although consensus guidelines and screening tools have been published for the evaluation and management of dementia in Down syndrome, it remains unclear if there has been widespread implementation of these,” the authors said.
Dr. Rafii is with the Alzheimer’s Therapeutic Research Institute at the University of Southern California, San Diego. Coauthor Dr. Santoro is with the Down Syndrome Program at Massachusetts General Hospital and with Harvard Medical School, both in Boston. The authors reported no conflict of interest disclosures related to their editorial, which appears in JAMA Neurology .
Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia, according to results of a recent prospective study.
More than 70% of the individuals with Down syndrome who died over the course of follow-up had a clinical diagnosis of dementia in this longitudinal study of community dwelling participants, many of whom had factors associated with dementia such as the apolipoprotein E (APOE) genotype.
The findings of this study support an “urgent need” for clinical trials of treatment that might delay or prevent dementia in individuals with Down syndrome, said the investigators, led by Rosalyn Hithersay, MSc, of the department of forensic and neurodevelopmental sciences in the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London (United Kingdom).
“We hope that our findings can improve clinical care by identifying factors associated with increased risk for dementia and mortality risk in this population, suggesting the potentially beneficial effects of existing medication options and helping clinicians provide prognostic information for their patients,” the authors wrote in JAMA Neurology.
The risk of dementia in individuals with Down syndrome has grown to “exceptional” levels, alongside a dramatic increase in life expectancy in these patients, from just 10 years of age some 50 years ago, to nearly 64 years today, investigators said.
Although other research has confirmed that dementia is frequently recorded as a contributory factor in Down syndrome deaths in recent years, this latest study provides crude mortality rates and exploratory analyses of factors that may modify mortality and dementia risk, according to the researchers.
Their study included 211 individuals with Down syndrome who were aged at least 36 years at study entry and followed for a total of 503.92 person-years, the investigators reported.
A total of 27 individuals died during follow-up, with a median age at death of 57 years; of those individuals, 19 (70.37%) had a clinical diagnosis of dementia, according to the report.
The crude mortality rate for individuals with dementia was nearly 1,192 deaths per 10,000 person-years, compared with 232 deaths per 10,000 person-years for those with no dementia diagnosis, the investigators found.
Further analysis showed that factors independently associated with mortality in those with a dementia diagnosis included APOE genotype, dementia medication status, early-onset epilepsy, and presence of two or more comorbid conditions.
In a combined model, APOE genotype was significantly associated with mortality risk, they added.
Among the eight individuals with Down syndrome who died without a dementia diagnosis, one reportedly had early signs of cognitive decline, and two had late-onset epilepsy.
Late-onset epilepsy, identified in seven individuals (4.8%) with no dementia diagnosis in this study, was the only factor associated with mortality in individuals without dementia, conferring a 10-fold increase in risk of that outcome, according to the analysis.
“This raises the question of whether seizures can begin in the absence of other features of dementia in individuals with Down syndrome or whether these seven individuals had significant AD pathology and neurological symptoms but had yet to receive a formal dementia diagnosis,” the researchers wrote in a discussion of results.
The authors reported no conflict of interest disclosures related to the study. Their research was supported by UK National Institute for Health Research networks and participating National Health Services trusts, as well as a Wellcome Trust Strategic Award to the London Down Syndrome Consortium.
SOURCE: Hithersay R et al. JAMA Neurol. 2018 Nov 19. doi: 10.1001/jamaneurol.2018.3616
Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia, according to results of a recent prospective study.
More than 70% of the individuals with Down syndrome who died over the course of follow-up had a clinical diagnosis of dementia in this longitudinal study of community dwelling participants, many of whom had factors associated with dementia such as the apolipoprotein E (APOE) genotype.
The findings of this study support an “urgent need” for clinical trials of treatment that might delay or prevent dementia in individuals with Down syndrome, said the investigators, led by Rosalyn Hithersay, MSc, of the department of forensic and neurodevelopmental sciences in the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London (United Kingdom).
“We hope that our findings can improve clinical care by identifying factors associated with increased risk for dementia and mortality risk in this population, suggesting the potentially beneficial effects of existing medication options and helping clinicians provide prognostic information for their patients,” the authors wrote in JAMA Neurology.
The risk of dementia in individuals with Down syndrome has grown to “exceptional” levels, alongside a dramatic increase in life expectancy in these patients, from just 10 years of age some 50 years ago, to nearly 64 years today, investigators said.
Although other research has confirmed that dementia is frequently recorded as a contributory factor in Down syndrome deaths in recent years, this latest study provides crude mortality rates and exploratory analyses of factors that may modify mortality and dementia risk, according to the researchers.
Their study included 211 individuals with Down syndrome who were aged at least 36 years at study entry and followed for a total of 503.92 person-years, the investigators reported.
A total of 27 individuals died during follow-up, with a median age at death of 57 years; of those individuals, 19 (70.37%) had a clinical diagnosis of dementia, according to the report.
The crude mortality rate for individuals with dementia was nearly 1,192 deaths per 10,000 person-years, compared with 232 deaths per 10,000 person-years for those with no dementia diagnosis, the investigators found.
Further analysis showed that factors independently associated with mortality in those with a dementia diagnosis included APOE genotype, dementia medication status, early-onset epilepsy, and presence of two or more comorbid conditions.
In a combined model, APOE genotype was significantly associated with mortality risk, they added.
Among the eight individuals with Down syndrome who died without a dementia diagnosis, one reportedly had early signs of cognitive decline, and two had late-onset epilepsy.
Late-onset epilepsy, identified in seven individuals (4.8%) with no dementia diagnosis in this study, was the only factor associated with mortality in individuals without dementia, conferring a 10-fold increase in risk of that outcome, according to the analysis.
“This raises the question of whether seizures can begin in the absence of other features of dementia in individuals with Down syndrome or whether these seven individuals had significant AD pathology and neurological symptoms but had yet to receive a formal dementia diagnosis,” the researchers wrote in a discussion of results.
The authors reported no conflict of interest disclosures related to the study. Their research was supported by UK National Institute for Health Research networks and participating National Health Services trusts, as well as a Wellcome Trust Strategic Award to the London Down Syndrome Consortium.
SOURCE: Hithersay R et al. JAMA Neurol. 2018 Nov 19. doi: 10.1001/jamaneurol.2018.3616
FROM JAMA NEUROLOGY
Key clinical point: Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia.
Major finding: The crude mortality rate for individuals with dementia versus those without dementia, respectively, was approximately 1,192 and 232 deaths per 10,000 person-years.
Study details: A prospective longitudinal study of 211 community-dwelling adults with Down syndrome in the United Kingdom.
Disclosures: Study authors reported no conflict of interest disclosures. The research was supported by National Institute for Health Research networks and participating National Health Services trusts, and a Wellcome Trust Strategic Award.
Source: Hithersay R et al. JAMA Neurol. 2018 Nov 19.
Second-melanoma risk higher with indoor tanning
than those who avoid indoor tanning, according to a retrospective study involving 434 melanoma patients.
The incidence of second melanomas over the entire 16-year course of the study was 25.2% among the tanning-bed users and 18.6% for nonusers. Among these study subjects – 27 with tanning-bed exposure and 61 without – median time to the second tumor was 225 days (0.62 years) for exposed patients and 1,280 days (3.50 years) for those with no exposure, the investigators reported.
This study, they wrote, is the first to show that “patients who had second primary melanoma diagnoses were more likely to have had” exposure to artificial UVR. The increased radiation intensity of tanning beds, “as opposed to UVR from ambient sunlight, in a physiologically vulnerable patient population [fair-skinned persons] at an early age contributes to our findings of decreased tumor lag time.”
SOURCE: Li Y et al. J Am Acad Dermatol. 2018;79(6):1101-8.
than those who avoid indoor tanning, according to a retrospective study involving 434 melanoma patients.
The incidence of second melanomas over the entire 16-year course of the study was 25.2% among the tanning-bed users and 18.6% for nonusers. Among these study subjects – 27 with tanning-bed exposure and 61 without – median time to the second tumor was 225 days (0.62 years) for exposed patients and 1,280 days (3.50 years) for those with no exposure, the investigators reported.
This study, they wrote, is the first to show that “patients who had second primary melanoma diagnoses were more likely to have had” exposure to artificial UVR. The increased radiation intensity of tanning beds, “as opposed to UVR from ambient sunlight, in a physiologically vulnerable patient population [fair-skinned persons] at an early age contributes to our findings of decreased tumor lag time.”
SOURCE: Li Y et al. J Am Acad Dermatol. 2018;79(6):1101-8.
than those who avoid indoor tanning, according to a retrospective study involving 434 melanoma patients.
The incidence of second melanomas over the entire 16-year course of the study was 25.2% among the tanning-bed users and 18.6% for nonusers. Among these study subjects – 27 with tanning-bed exposure and 61 without – median time to the second tumor was 225 days (0.62 years) for exposed patients and 1,280 days (3.50 years) for those with no exposure, the investigators reported.
This study, they wrote, is the first to show that “patients who had second primary melanoma diagnoses were more likely to have had” exposure to artificial UVR. The increased radiation intensity of tanning beds, “as opposed to UVR from ambient sunlight, in a physiologically vulnerable patient population [fair-skinned persons] at an early age contributes to our findings of decreased tumor lag time.”
SOURCE: Li Y et al. J Am Acad Dermatol. 2018;79(6):1101-8.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Levonorgestrel implant right after delivery does not affect breastfeeding, infant growth
Researchers found no significant differences in infant growth, changes in breastfeeding initiation or breastfeeding continuation at 3-month and 6-month follow-up among women who received a levonorgestrel contraception implant very soon after delivery, compared with women who waited to receive the implant.
“These findings are consistent with the preponderance of literature supporting the hypothesis that progestin-containing contraceptives do not compromise a woman’s ability to initiate or sustain breastfeeding and do not adversely affect infant growth,” Sarah Averbach, MD, of the University of California, San Francisco, and her colleagues wrote in their study published in Contraception.
Dr. Averbach and her colleagues randomized 96 women to receive a two-rod levonorgestrel (LNG)–releasing subdermal contraceptive implant within 5 days of delivery (mean time, 36 hours post delivery) and 87 women to delay the implant to between 6 and 8 weeks at a postpartum follow-up visit (mean time, 68 days). The women were a minimum of 18 years old with a recent vaginal or cesarean section delivery at a Ugandan hospital; 55% of the women had at least three children, and 73% said they had prior experience breastfeeding. The researchers then examined infant weight change and infant head circumference change at 6 months from birth, time to lactogenesis, and whether mothers continued to breastfeed at 3 months and 6 months after birth.
Infant weight was similar in the immediate-implant group (4,632 g), compared with the delayed-implant group (4,407 g; P = .26); infant head circumference was similar between both groups (9.3 cm vs. 9.5 cm; P = .70) at 6 months as well. The time to lactogenesis was not significantly different in the immediate-implant (65 hours) and delayed-implant (63 hours; P = .84) groups. At 3 months, 74% of immediate-implant participants and 71% of delayed-implant participants said they were breastfeeding exclusively (P = .74); at 6 months, 48% of immediate implant participants and 52% of delayed implant participants reported exclusive breastfeeding (P equals .58).
Limitations of the study included follow-up to only 6 months and selection of participants with previous breastfeeding experience. Researchers also noted better measurements of infant and maternal breast milk intake also could be used and limit generalization of the results.
This study was funded by the Society of Family Planning Research Fund. Dr. Averbach is supported by an award from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The other authors had no relevant financial disclosures.
SOURCE: Averbach S et al. Contraception. 2018. doi: 10.1016/j.contraception.2018.10.008.
Researchers found no significant differences in infant growth, changes in breastfeeding initiation or breastfeeding continuation at 3-month and 6-month follow-up among women who received a levonorgestrel contraception implant very soon after delivery, compared with women who waited to receive the implant.
“These findings are consistent with the preponderance of literature supporting the hypothesis that progestin-containing contraceptives do not compromise a woman’s ability to initiate or sustain breastfeeding and do not adversely affect infant growth,” Sarah Averbach, MD, of the University of California, San Francisco, and her colleagues wrote in their study published in Contraception.
Dr. Averbach and her colleagues randomized 96 women to receive a two-rod levonorgestrel (LNG)–releasing subdermal contraceptive implant within 5 days of delivery (mean time, 36 hours post delivery) and 87 women to delay the implant to between 6 and 8 weeks at a postpartum follow-up visit (mean time, 68 days). The women were a minimum of 18 years old with a recent vaginal or cesarean section delivery at a Ugandan hospital; 55% of the women had at least three children, and 73% said they had prior experience breastfeeding. The researchers then examined infant weight change and infant head circumference change at 6 months from birth, time to lactogenesis, and whether mothers continued to breastfeed at 3 months and 6 months after birth.
Infant weight was similar in the immediate-implant group (4,632 g), compared with the delayed-implant group (4,407 g; P = .26); infant head circumference was similar between both groups (9.3 cm vs. 9.5 cm; P = .70) at 6 months as well. The time to lactogenesis was not significantly different in the immediate-implant (65 hours) and delayed-implant (63 hours; P = .84) groups. At 3 months, 74% of immediate-implant participants and 71% of delayed-implant participants said they were breastfeeding exclusively (P = .74); at 6 months, 48% of immediate implant participants and 52% of delayed implant participants reported exclusive breastfeeding (P equals .58).
Limitations of the study included follow-up to only 6 months and selection of participants with previous breastfeeding experience. Researchers also noted better measurements of infant and maternal breast milk intake also could be used and limit generalization of the results.
This study was funded by the Society of Family Planning Research Fund. Dr. Averbach is supported by an award from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The other authors had no relevant financial disclosures.
SOURCE: Averbach S et al. Contraception. 2018. doi: 10.1016/j.contraception.2018.10.008.
Researchers found no significant differences in infant growth, changes in breastfeeding initiation or breastfeeding continuation at 3-month and 6-month follow-up among women who received a levonorgestrel contraception implant very soon after delivery, compared with women who waited to receive the implant.
“These findings are consistent with the preponderance of literature supporting the hypothesis that progestin-containing contraceptives do not compromise a woman’s ability to initiate or sustain breastfeeding and do not adversely affect infant growth,” Sarah Averbach, MD, of the University of California, San Francisco, and her colleagues wrote in their study published in Contraception.
Dr. Averbach and her colleagues randomized 96 women to receive a two-rod levonorgestrel (LNG)–releasing subdermal contraceptive implant within 5 days of delivery (mean time, 36 hours post delivery) and 87 women to delay the implant to between 6 and 8 weeks at a postpartum follow-up visit (mean time, 68 days). The women were a minimum of 18 years old with a recent vaginal or cesarean section delivery at a Ugandan hospital; 55% of the women had at least three children, and 73% said they had prior experience breastfeeding. The researchers then examined infant weight change and infant head circumference change at 6 months from birth, time to lactogenesis, and whether mothers continued to breastfeed at 3 months and 6 months after birth.
Infant weight was similar in the immediate-implant group (4,632 g), compared with the delayed-implant group (4,407 g; P = .26); infant head circumference was similar between both groups (9.3 cm vs. 9.5 cm; P = .70) at 6 months as well. The time to lactogenesis was not significantly different in the immediate-implant (65 hours) and delayed-implant (63 hours; P = .84) groups. At 3 months, 74% of immediate-implant participants and 71% of delayed-implant participants said they were breastfeeding exclusively (P = .74); at 6 months, 48% of immediate implant participants and 52% of delayed implant participants reported exclusive breastfeeding (P equals .58).
Limitations of the study included follow-up to only 6 months and selection of participants with previous breastfeeding experience. Researchers also noted better measurements of infant and maternal breast milk intake also could be used and limit generalization of the results.
This study was funded by the Society of Family Planning Research Fund. Dr. Averbach is supported by an award from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The other authors had no relevant financial disclosures.
SOURCE: Averbach S et al. Contraception. 2018. doi: 10.1016/j.contraception.2018.10.008.
FROM CONTRACEPTION
Key clinical point:
Major finding: Infant weight was similar in the immediate-implant group (4,632 g), compared with the delayed-implant group (4,407 g; P = .26); infant head circumference was similar between both groups (9.3 cm vs. 9.5 cm; P = .70) at 6 months as well.
Study details: A randomized trial of 96 women in Uganda who received a contraceptive implant less than 5 days after delivery and 86 women who received the implant between 6 and 8 weeks post partum.
Disclosures: This study was funded by the Society of Family Planning Research Fund. Dr. Averbach is supported by an award from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The other authors had no relevant financial disclosures.
Source: Averbach S et al. Contraception. 2018. doi: 10.1016/j.contraception.2018.10.008.
Treating psoriasis with biologics: Recommendations from an expert
LAS VEGAS – If you’re considering adding biologics for psoriasis to your clinical practice, dermatologist Kristina C. Duffin, MD, has some advice: Don’t expect to just use one drug, focus on comorbidities, and embrace strategies to bypass the potential obstacle of prior-authorization approvals.
Here are some tips from Dr. Duffin, who spoke at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:
- Don’t expect a one-size-fits-all medication. “There is no one, single go-to drug,” said Dr. Duffin, who is cochair of the department of dermatology at the University of Utah, Salt Lake City. “Maybe someday, we will have a biological personalized medicine marker to say this is the right drug, but for now we don’t.” More than 10 biologics are available to treat psoriasis, she said, and more are in the pipeline.
- Pay close attention to comorbidities. It’s important to “have a good grasp” of a patient’s comorbidities, which can help focus the choice of a biologic, Dr. Duffin said. She recommends starting with an anti–tumor necrosis factor (TNF) agents for patients with psoriatic arthritis. For patients with Crohn’s disease, she recommends anti-TNF (adalimumab, infliximab) and anti-interleukin–12/23 or anti-IL-23 agents (ustekinumab). Anti-TNF agents should be avoided in patients with multiple sclerosis, and anti-IL-17 agents shouldn’t be given to patients with recurrent candidiasis, she noted.
- Encourage patients to make prompt decisions. Dr. Duffin sits down with patients to discuss various biologic options, and she goes over information in handouts. She also focuses on their needs: “Are they interested in getting better fast? Do they want to be clear for their wedding in a month?” She prefers to not let patients go home to think about what they’d like to do. Instead, she advises patients to make choices while at the office visit.
- Order lab tests and be careful about vaccines. Dr. Duffin orders the following tests for all patients who are starting on biologics: CBC, comprehensive metabolic panel, hepatitis B and C, and tuberculosis. She orders HIV, Hba1c and lipid tests, if appropriate. She prefers that patients treated with biologics avoid live vaccines. She suggests other vaccines, if indicated, such as seasonal influenza and pneumonia vaccines, and for those aged 50 years and older, herpes zoster vaccine. She urges patients to call the office if they have an infection or need surgery because they may need to discuss putting a temporary hold on the biologics.
- Understand how to navigate formularies.“Getting drugs approved for patients with Medicare is a challenge,” Dr. Duffin said. It’s helpful to understand how insurers handle specific psoriasis drugs so you can choose one that’s likely to be covered if you’re unsure which one is best. The website www.covermymeds.com allows physicians to easily check insurer formularies, free of charge, she said.
- Documentation is crucial when you’re dealing with an insurer. Document body surface area, Psoriasis Area Severity Index scores, or physician global assessment measures, she advised. An app provided by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, is a helpful in determining these measurements, she said. Also include information about failed treatments and the rationale behind why you chose a specific treatment, she said. “If denial happens, get the details,” she said. This may turn up a clerical error on the insurer’s part that incorrectly led to a denial.
- Escalate challenges to drug denials. If the preferred treatment is denied, one option is to appeal the denial. As a resource, Dr. Duffin pointed to sample letters for appealing denials for physicians and patients on the websites for the American Academy of Dermatology and the National Psoriasis Foundation. Ask for a limited 6-month approval, she said, or have the patient write a letter to the insurer using one of the sample letter templates. Another option is to ask the insurer for a “peer-to-peer” review, she said. “Sometimes it’s really hard for insurance company folks to say no to you if you have a really good story,” she commented.
- Help your patients get financial assistance. Almost every biologic manufacturer has a patient assistance plan, which can also help with deductibles and copays, Dr. Duffin said.
Dr. Duffin discloses consulting for AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, and Sienna. She has received grant/contracted research support from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sienna, Stiefel, and UCB.
SDEF and this news organization are owned by the same parent company.
LAS VEGAS – If you’re considering adding biologics for psoriasis to your clinical practice, dermatologist Kristina C. Duffin, MD, has some advice: Don’t expect to just use one drug, focus on comorbidities, and embrace strategies to bypass the potential obstacle of prior-authorization approvals.
Here are some tips from Dr. Duffin, who spoke at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:
- Don’t expect a one-size-fits-all medication. “There is no one, single go-to drug,” said Dr. Duffin, who is cochair of the department of dermatology at the University of Utah, Salt Lake City. “Maybe someday, we will have a biological personalized medicine marker to say this is the right drug, but for now we don’t.” More than 10 biologics are available to treat psoriasis, she said, and more are in the pipeline.
- Pay close attention to comorbidities. It’s important to “have a good grasp” of a patient’s comorbidities, which can help focus the choice of a biologic, Dr. Duffin said. She recommends starting with an anti–tumor necrosis factor (TNF) agents for patients with psoriatic arthritis. For patients with Crohn’s disease, she recommends anti-TNF (adalimumab, infliximab) and anti-interleukin–12/23 or anti-IL-23 agents (ustekinumab). Anti-TNF agents should be avoided in patients with multiple sclerosis, and anti-IL-17 agents shouldn’t be given to patients with recurrent candidiasis, she noted.
- Encourage patients to make prompt decisions. Dr. Duffin sits down with patients to discuss various biologic options, and she goes over information in handouts. She also focuses on their needs: “Are they interested in getting better fast? Do they want to be clear for their wedding in a month?” She prefers to not let patients go home to think about what they’d like to do. Instead, she advises patients to make choices while at the office visit.
- Order lab tests and be careful about vaccines. Dr. Duffin orders the following tests for all patients who are starting on biologics: CBC, comprehensive metabolic panel, hepatitis B and C, and tuberculosis. She orders HIV, Hba1c and lipid tests, if appropriate. She prefers that patients treated with biologics avoid live vaccines. She suggests other vaccines, if indicated, such as seasonal influenza and pneumonia vaccines, and for those aged 50 years and older, herpes zoster vaccine. She urges patients to call the office if they have an infection or need surgery because they may need to discuss putting a temporary hold on the biologics.
- Understand how to navigate formularies.“Getting drugs approved for patients with Medicare is a challenge,” Dr. Duffin said. It’s helpful to understand how insurers handle specific psoriasis drugs so you can choose one that’s likely to be covered if you’re unsure which one is best. The website www.covermymeds.com allows physicians to easily check insurer formularies, free of charge, she said.
- Documentation is crucial when you’re dealing with an insurer. Document body surface area, Psoriasis Area Severity Index scores, or physician global assessment measures, she advised. An app provided by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, is a helpful in determining these measurements, she said. Also include information about failed treatments and the rationale behind why you chose a specific treatment, she said. “If denial happens, get the details,” she said. This may turn up a clerical error on the insurer’s part that incorrectly led to a denial.
- Escalate challenges to drug denials. If the preferred treatment is denied, one option is to appeal the denial. As a resource, Dr. Duffin pointed to sample letters for appealing denials for physicians and patients on the websites for the American Academy of Dermatology and the National Psoriasis Foundation. Ask for a limited 6-month approval, she said, or have the patient write a letter to the insurer using one of the sample letter templates. Another option is to ask the insurer for a “peer-to-peer” review, she said. “Sometimes it’s really hard for insurance company folks to say no to you if you have a really good story,” she commented.
- Help your patients get financial assistance. Almost every biologic manufacturer has a patient assistance plan, which can also help with deductibles and copays, Dr. Duffin said.
Dr. Duffin discloses consulting for AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, and Sienna. She has received grant/contracted research support from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sienna, Stiefel, and UCB.
SDEF and this news organization are owned by the same parent company.
LAS VEGAS – If you’re considering adding biologics for psoriasis to your clinical practice, dermatologist Kristina C. Duffin, MD, has some advice: Don’t expect to just use one drug, focus on comorbidities, and embrace strategies to bypass the potential obstacle of prior-authorization approvals.
Here are some tips from Dr. Duffin, who spoke at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:
- Don’t expect a one-size-fits-all medication. “There is no one, single go-to drug,” said Dr. Duffin, who is cochair of the department of dermatology at the University of Utah, Salt Lake City. “Maybe someday, we will have a biological personalized medicine marker to say this is the right drug, but for now we don’t.” More than 10 biologics are available to treat psoriasis, she said, and more are in the pipeline.
- Pay close attention to comorbidities. It’s important to “have a good grasp” of a patient’s comorbidities, which can help focus the choice of a biologic, Dr. Duffin said. She recommends starting with an anti–tumor necrosis factor (TNF) agents for patients with psoriatic arthritis. For patients with Crohn’s disease, she recommends anti-TNF (adalimumab, infliximab) and anti-interleukin–12/23 or anti-IL-23 agents (ustekinumab). Anti-TNF agents should be avoided in patients with multiple sclerosis, and anti-IL-17 agents shouldn’t be given to patients with recurrent candidiasis, she noted.
- Encourage patients to make prompt decisions. Dr. Duffin sits down with patients to discuss various biologic options, and she goes over information in handouts. She also focuses on their needs: “Are they interested in getting better fast? Do they want to be clear for their wedding in a month?” She prefers to not let patients go home to think about what they’d like to do. Instead, she advises patients to make choices while at the office visit.
- Order lab tests and be careful about vaccines. Dr. Duffin orders the following tests for all patients who are starting on biologics: CBC, comprehensive metabolic panel, hepatitis B and C, and tuberculosis. She orders HIV, Hba1c and lipid tests, if appropriate. She prefers that patients treated with biologics avoid live vaccines. She suggests other vaccines, if indicated, such as seasonal influenza and pneumonia vaccines, and for those aged 50 years and older, herpes zoster vaccine. She urges patients to call the office if they have an infection or need surgery because they may need to discuss putting a temporary hold on the biologics.
- Understand how to navigate formularies.“Getting drugs approved for patients with Medicare is a challenge,” Dr. Duffin said. It’s helpful to understand how insurers handle specific psoriasis drugs so you can choose one that’s likely to be covered if you’re unsure which one is best. The website www.covermymeds.com allows physicians to easily check insurer formularies, free of charge, she said.
- Documentation is crucial when you’re dealing with an insurer. Document body surface area, Psoriasis Area Severity Index scores, or physician global assessment measures, she advised. An app provided by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, is a helpful in determining these measurements, she said. Also include information about failed treatments and the rationale behind why you chose a specific treatment, she said. “If denial happens, get the details,” she said. This may turn up a clerical error on the insurer’s part that incorrectly led to a denial.
- Escalate challenges to drug denials. If the preferred treatment is denied, one option is to appeal the denial. As a resource, Dr. Duffin pointed to sample letters for appealing denials for physicians and patients on the websites for the American Academy of Dermatology and the National Psoriasis Foundation. Ask for a limited 6-month approval, she said, or have the patient write a letter to the insurer using one of the sample letter templates. Another option is to ask the insurer for a “peer-to-peer” review, she said. “Sometimes it’s really hard for insurance company folks to say no to you if you have a really good story,” she commented.
- Help your patients get financial assistance. Almost every biologic manufacturer has a patient assistance plan, which can also help with deductibles and copays, Dr. Duffin said.
Dr. Duffin discloses consulting for AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, and Sienna. She has received grant/contracted research support from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sienna, Stiefel, and UCB.
SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF LAS VEGAS DERMATOLOGY SEMINAR
Intimate partner violence and PTSD increase menopausal symptom risk
Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.
Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.
Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.
Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.
Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.
Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.
“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.
The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.
“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.
Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.
The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.
An estimated 33% of women in the United States have been sexually assaulted, and an estimated 25% have experienced IPV, so be aware of how common this “wicked problem” is, the way it impacts health, and what role you can play in educating and helping patients by connecting them to available resources.
But that is not enough. Consider measures such as training yourself and staff in how to assess for IPV and sexual assault and use of EHR to integrate IPV assessment into routine clinical care, as well as developing protocols to be followed when a patient discloses IPV or sexual assault. A multidisciplinary approach also can help, including victim service advocates and behavioral health clinicians to provide care and support.
State requirements for reporting partner and sexual violence differ, so be aware of your state laws.
A strength of this study is that it included emotional as well as physical IPV, which often is left out although it has serious impacts.
Rebecca C. Thurston, PhD, is from the department of psychiatry at the University of Pittsburgh, and Elizabeth Miller, MD, PhD, is from the division of adolescent and young adult medicine at the UPMC Children’s Hospital of Pittsburgh. These comments were taken from an accompanying editorial (JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5242). Dr. Thurston declared research support from the National Institutes of Health and consultancies for Pfizer, Procter & Gamble, and MAS Innovations.
An estimated 33% of women in the United States have been sexually assaulted, and an estimated 25% have experienced IPV, so be aware of how common this “wicked problem” is, the way it impacts health, and what role you can play in educating and helping patients by connecting them to available resources.
But that is not enough. Consider measures such as training yourself and staff in how to assess for IPV and sexual assault and use of EHR to integrate IPV assessment into routine clinical care, as well as developing protocols to be followed when a patient discloses IPV or sexual assault. A multidisciplinary approach also can help, including victim service advocates and behavioral health clinicians to provide care and support.
State requirements for reporting partner and sexual violence differ, so be aware of your state laws.
A strength of this study is that it included emotional as well as physical IPV, which often is left out although it has serious impacts.
Rebecca C. Thurston, PhD, is from the department of psychiatry at the University of Pittsburgh, and Elizabeth Miller, MD, PhD, is from the division of adolescent and young adult medicine at the UPMC Children’s Hospital of Pittsburgh. These comments were taken from an accompanying editorial (JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5242). Dr. Thurston declared research support from the National Institutes of Health and consultancies for Pfizer, Procter & Gamble, and MAS Innovations.
An estimated 33% of women in the United States have been sexually assaulted, and an estimated 25% have experienced IPV, so be aware of how common this “wicked problem” is, the way it impacts health, and what role you can play in educating and helping patients by connecting them to available resources.
But that is not enough. Consider measures such as training yourself and staff in how to assess for IPV and sexual assault and use of EHR to integrate IPV assessment into routine clinical care, as well as developing protocols to be followed when a patient discloses IPV or sexual assault. A multidisciplinary approach also can help, including victim service advocates and behavioral health clinicians to provide care and support.
State requirements for reporting partner and sexual violence differ, so be aware of your state laws.
A strength of this study is that it included emotional as well as physical IPV, which often is left out although it has serious impacts.
Rebecca C. Thurston, PhD, is from the department of psychiatry at the University of Pittsburgh, and Elizabeth Miller, MD, PhD, is from the division of adolescent and young adult medicine at the UPMC Children’s Hospital of Pittsburgh. These comments were taken from an accompanying editorial (JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5242). Dr. Thurston declared research support from the National Institutes of Health and consultancies for Pfizer, Procter & Gamble, and MAS Innovations.
Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.
Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.
Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.
Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.
Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.
Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.
“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.
The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.
“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.
Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.
The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.
Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.
Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.
Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.
Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.
Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.
Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.
“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.
The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.
“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.
Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.
The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Intimate partner violence increases the risk of menopausal symptoms.
Major finding:
Study details: A cohort study in 2,016 women aged 40 years and older.
Disclosures: The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
Source: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi:10.1001/jamainternmed.2018.5233.
Advancements in the Delivery of Biologics for the Treatment of Diabetes
Diabetes medication administration often forces patients into uncomfortable situations. Those with complicated treatment or with a fear of needles might hesitate to adhere to their suggested regimen, placing themselves at risk. Over the years, several mechanisms have evolved to help make insulin delivery, and so, betting patient adherence.
This fifth eNewsletter in the series, entitled Advancements in the Delivery of Biologics for the Treatment of Diabetes was written by James Ruggles, PhD, and James Meehan, MSc. It covers the history of insulin delivery methods starting from 1922 and through present day.
Click here to read the supplement
About the Authors:
James Ruggles, PhD
AstraZeneca
Wilmington, DE, USA
James Meehan, MSc
AstraZeneca
Macclesfield, Cheshire, UK
Diabetes medication administration often forces patients into uncomfortable situations. Those with complicated treatment or with a fear of needles might hesitate to adhere to their suggested regimen, placing themselves at risk. Over the years, several mechanisms have evolved to help make insulin delivery, and so, betting patient adherence.
This fifth eNewsletter in the series, entitled Advancements in the Delivery of Biologics for the Treatment of Diabetes was written by James Ruggles, PhD, and James Meehan, MSc. It covers the history of insulin delivery methods starting from 1922 and through present day.
Click here to read the supplement
About the Authors:
James Ruggles, PhD
AstraZeneca
Wilmington, DE, USA
James Meehan, MSc
AstraZeneca
Macclesfield, Cheshire, UK
Diabetes medication administration often forces patients into uncomfortable situations. Those with complicated treatment or with a fear of needles might hesitate to adhere to their suggested regimen, placing themselves at risk. Over the years, several mechanisms have evolved to help make insulin delivery, and so, betting patient adherence.
This fifth eNewsletter in the series, entitled Advancements in the Delivery of Biologics for the Treatment of Diabetes was written by James Ruggles, PhD, and James Meehan, MSc. It covers the history of insulin delivery methods starting from 1922 and through present day.
Click here to read the supplement
About the Authors:
James Ruggles, PhD
AstraZeneca
Wilmington, DE, USA
James Meehan, MSc
AstraZeneca
Macclesfield, Cheshire, UK
Leg ulceration guidelines expected to soon include endovascular ablation
NEW YORK – Guidelines for the management of leg ulcerations will be changed to accommodate the results of the Early Venous Reflux Ablation trial, according to this video interview with the senior author, Alun H Davies, DSc, professor of vascular surgery, Imperial College, London.
In this video interview, conducted at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation, Dr. Davies recaps the major results of the study, which associated immediate endovascular ablation (early intervention) with significantly faster healing than did compression therapy with ablation, considered only after 6 months (delayed intervention).
These data have been published (N Engl J Med 2018 May 31;378:2105-14), but Dr. Davies focused in this interview on the cost efficacy of early intervention with endovascular ablation. In the United Kingdom, where the study was conducted, the data support the cost efficacy, but Dr. Davies predicted even greater savings in the United States because of the expense of frequent wound care visits.
Based on data from a randomized trial, he expects guidelines, including those in the United States, to be revised to list early endovascular ablation as a 1b or 1A recommendation, thereby establishing this intervention as a standard.
If follow-up after 3 years confirms a lower rate of recurrence, an advantage previously shown for open surgery relative to compression healing, the case for early endovascular intervention will be even stronger, according to Dr. Davies.
NEW YORK – Guidelines for the management of leg ulcerations will be changed to accommodate the results of the Early Venous Reflux Ablation trial, according to this video interview with the senior author, Alun H Davies, DSc, professor of vascular surgery, Imperial College, London.
In this video interview, conducted at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation, Dr. Davies recaps the major results of the study, which associated immediate endovascular ablation (early intervention) with significantly faster healing than did compression therapy with ablation, considered only after 6 months (delayed intervention).
These data have been published (N Engl J Med 2018 May 31;378:2105-14), but Dr. Davies focused in this interview on the cost efficacy of early intervention with endovascular ablation. In the United Kingdom, where the study was conducted, the data support the cost efficacy, but Dr. Davies predicted even greater savings in the United States because of the expense of frequent wound care visits.
Based on data from a randomized trial, he expects guidelines, including those in the United States, to be revised to list early endovascular ablation as a 1b or 1A recommendation, thereby establishing this intervention as a standard.
If follow-up after 3 years confirms a lower rate of recurrence, an advantage previously shown for open surgery relative to compression healing, the case for early endovascular intervention will be even stronger, according to Dr. Davies.
NEW YORK – Guidelines for the management of leg ulcerations will be changed to accommodate the results of the Early Venous Reflux Ablation trial, according to this video interview with the senior author, Alun H Davies, DSc, professor of vascular surgery, Imperial College, London.
In this video interview, conducted at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation, Dr. Davies recaps the major results of the study, which associated immediate endovascular ablation (early intervention) with significantly faster healing than did compression therapy with ablation, considered only after 6 months (delayed intervention).
These data have been published (N Engl J Med 2018 May 31;378:2105-14), but Dr. Davies focused in this interview on the cost efficacy of early intervention with endovascular ablation. In the United Kingdom, where the study was conducted, the data support the cost efficacy, but Dr. Davies predicted even greater savings in the United States because of the expense of frequent wound care visits.
Based on data from a randomized trial, he expects guidelines, including those in the United States, to be revised to list early endovascular ablation as a 1b or 1A recommendation, thereby establishing this intervention as a standard.
If follow-up after 3 years confirms a lower rate of recurrence, an advantage previously shown for open surgery relative to compression healing, the case for early endovascular intervention will be even stronger, according to Dr. Davies.
REPORTING FROM VEITHSYMPOSIUM
Empagliflozin reduces left ventricular mass
CHICAGO – Empagliflozin significantly reduced left ventricular mass compared with placebo over the course of 6 months in patients with type 2 diabetes and stable coronary artery disease in the randomized EMPA-HEART CardioLink-6 trial.
Use of empagliflozin (Jardiance), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), also was associated with a clinically meaningful reduction in ambulatory systolic blood pressure and a boost in hematocrit in this population of normotensive patients with preserved left ventricular ejection fraction and high utilization of background guideline-directed medical therapy, Subodh Verma, MD, reported at the American Heart Association scientific sessions.
“Taken together, these data suggest that empagliflozin promotes early statistically and clinically significant reverse remodeling, which may contribute to the cardiovascular and heart failure benefits observed in the EMPA-REG OUTCOME trial and other SGLT2i studies,” added Dr. Verma, professor of surgery, pharmacology, and toxicology at the University of Toronto.
EMPA-REG OUTCOME was a landmark randomized trial that included 7,020 patients with type 2 diabetes and established ischemic cardiovascular disease in which the SGLT2i reduced all-cause mortality by 32%, compared with placebo over a median 3.1 years of follow-up, cardiovascular mortality by 38%, and hospitalizations for heart failure by 35% (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
The mechanism responsible for these impressive clinical benefits has been unclear. The EMPA-HEART CardioLink-6 trial was a small study – 97 randomized patients – designed to shed light on this issue. The hypothesis was that SGLT2i therapy facilitates cardiac reverse remodeling. This indeed turned out to be the case when cardiac MRI findings at baseline and after 6 months were compared by blinded evaluators.
From a baseline mean left ventricular mass indexed to body surface area of 60 g/m2, which is within normal range, left ventricular mass decreased by a mean of 4.71 g in the empagliflozin group, compared with a mere 0.39-g reduction in placebo-treated controls.
Dr. Verma underscored the importance of this result: “Left ventricular mass is a strong and independent predictor of major cardiovascular events, including cardiovascular and all-cause mortality, myocardial infarction, and heart failure. Furthermore, the magnitude of left ventricular mass regression correlates with the extent of clinical outcome benefit seen with pharmacological and device therapies.”
In a prespecified subgroup analysis stratified by baseline LV mass index, patients with a baseline value greater than 60 g/m2 experienced a much greater benefit from empagliflozin, with a mean between-group difference in LV mass index reduction of 7.26 g/m2, compared with a 0.46-g/m2 difference between the SGLT2i and placebo among those with a baseline LV mass index of 60 g/m2 or less.
Ambulatory systolic blood pressure fell from a baseline of 139 mm Hg by a mean of 7.9 mm Hg in the empagliflozin group and 0.7 mm Hg with placebo. From a baseline hematocrit of 42%, hematocrit improved by an absolute 1.91% more with empagliflozin than placebo. However, there were no significant between-group differences in the secondary cardiac MRI outcomes of change in LV end-systolic volume index, LV end-diastolic volume index, or LV ejection fraction.
Discussant Elliott M. Antman, MD, hailed EMPA-HEART CardioLink-6 as “a very important mechanistic study.”
“As I leave Chicago for home, I plan to further increase the use of SGLT2 inhibitors in my patients with type 2 diabetes, especially if they have a history of heart failure, and especially if they have coronary artery disease. I would encourage you to think about doing the same, and I would also recommend that we urge our colleagues in general medicine, endocrinology, and nephrology to consider this information as well,” said Dr. Antman, professor of medicine and associate dean for clinical and translational research at Harvard Medical School, Boston, as well as an AHA past president.
He noted that EMPA-HEART CardioLink-6 provides “biologically plausible data” to explain the mechanism for the major clinical benefits of empagliflozin earlier documented in EMPA-REG OUTCOME. The likely driver of the reduction in left ventricular mass seen in EMPA-HEART CardioLink-6 was the combination of lower systolic blood pressure and higher hematocrit.
“These surrogates suggest that our traditional concepts of afterload and preload appear to be favorably affected by SGLT2 inhibition,” according to the cardiologist.
The EMPA-HEART CardioLink-6 study was funded by Boehringer Ingelheim. Dr. Verma reported receiving research support and/or speaker payments from that pharmaceutical company and roughly a dozen others. Dr. Antman had no disclosures.
SOURCE: Verma S. AHA 2018, Abstract 19332.
CHICAGO – Empagliflozin significantly reduced left ventricular mass compared with placebo over the course of 6 months in patients with type 2 diabetes and stable coronary artery disease in the randomized EMPA-HEART CardioLink-6 trial.
Use of empagliflozin (Jardiance), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), also was associated with a clinically meaningful reduction in ambulatory systolic blood pressure and a boost in hematocrit in this population of normotensive patients with preserved left ventricular ejection fraction and high utilization of background guideline-directed medical therapy, Subodh Verma, MD, reported at the American Heart Association scientific sessions.
“Taken together, these data suggest that empagliflozin promotes early statistically and clinically significant reverse remodeling, which may contribute to the cardiovascular and heart failure benefits observed in the EMPA-REG OUTCOME trial and other SGLT2i studies,” added Dr. Verma, professor of surgery, pharmacology, and toxicology at the University of Toronto.
EMPA-REG OUTCOME was a landmark randomized trial that included 7,020 patients with type 2 diabetes and established ischemic cardiovascular disease in which the SGLT2i reduced all-cause mortality by 32%, compared with placebo over a median 3.1 years of follow-up, cardiovascular mortality by 38%, and hospitalizations for heart failure by 35% (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
The mechanism responsible for these impressive clinical benefits has been unclear. The EMPA-HEART CardioLink-6 trial was a small study – 97 randomized patients – designed to shed light on this issue. The hypothesis was that SGLT2i therapy facilitates cardiac reverse remodeling. This indeed turned out to be the case when cardiac MRI findings at baseline and after 6 months were compared by blinded evaluators.
From a baseline mean left ventricular mass indexed to body surface area of 60 g/m2, which is within normal range, left ventricular mass decreased by a mean of 4.71 g in the empagliflozin group, compared with a mere 0.39-g reduction in placebo-treated controls.
Dr. Verma underscored the importance of this result: “Left ventricular mass is a strong and independent predictor of major cardiovascular events, including cardiovascular and all-cause mortality, myocardial infarction, and heart failure. Furthermore, the magnitude of left ventricular mass regression correlates with the extent of clinical outcome benefit seen with pharmacological and device therapies.”
In a prespecified subgroup analysis stratified by baseline LV mass index, patients with a baseline value greater than 60 g/m2 experienced a much greater benefit from empagliflozin, with a mean between-group difference in LV mass index reduction of 7.26 g/m2, compared with a 0.46-g/m2 difference between the SGLT2i and placebo among those with a baseline LV mass index of 60 g/m2 or less.
Ambulatory systolic blood pressure fell from a baseline of 139 mm Hg by a mean of 7.9 mm Hg in the empagliflozin group and 0.7 mm Hg with placebo. From a baseline hematocrit of 42%, hematocrit improved by an absolute 1.91% more with empagliflozin than placebo. However, there were no significant between-group differences in the secondary cardiac MRI outcomes of change in LV end-systolic volume index, LV end-diastolic volume index, or LV ejection fraction.
Discussant Elliott M. Antman, MD, hailed EMPA-HEART CardioLink-6 as “a very important mechanistic study.”
“As I leave Chicago for home, I plan to further increase the use of SGLT2 inhibitors in my patients with type 2 diabetes, especially if they have a history of heart failure, and especially if they have coronary artery disease. I would encourage you to think about doing the same, and I would also recommend that we urge our colleagues in general medicine, endocrinology, and nephrology to consider this information as well,” said Dr. Antman, professor of medicine and associate dean for clinical and translational research at Harvard Medical School, Boston, as well as an AHA past president.
He noted that EMPA-HEART CardioLink-6 provides “biologically plausible data” to explain the mechanism for the major clinical benefits of empagliflozin earlier documented in EMPA-REG OUTCOME. The likely driver of the reduction in left ventricular mass seen in EMPA-HEART CardioLink-6 was the combination of lower systolic blood pressure and higher hematocrit.
“These surrogates suggest that our traditional concepts of afterload and preload appear to be favorably affected by SGLT2 inhibition,” according to the cardiologist.
The EMPA-HEART CardioLink-6 study was funded by Boehringer Ingelheim. Dr. Verma reported receiving research support and/or speaker payments from that pharmaceutical company and roughly a dozen others. Dr. Antman had no disclosures.
SOURCE: Verma S. AHA 2018, Abstract 19332.
CHICAGO – Empagliflozin significantly reduced left ventricular mass compared with placebo over the course of 6 months in patients with type 2 diabetes and stable coronary artery disease in the randomized EMPA-HEART CardioLink-6 trial.
Use of empagliflozin (Jardiance), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), also was associated with a clinically meaningful reduction in ambulatory systolic blood pressure and a boost in hematocrit in this population of normotensive patients with preserved left ventricular ejection fraction and high utilization of background guideline-directed medical therapy, Subodh Verma, MD, reported at the American Heart Association scientific sessions.
“Taken together, these data suggest that empagliflozin promotes early statistically and clinically significant reverse remodeling, which may contribute to the cardiovascular and heart failure benefits observed in the EMPA-REG OUTCOME trial and other SGLT2i studies,” added Dr. Verma, professor of surgery, pharmacology, and toxicology at the University of Toronto.
EMPA-REG OUTCOME was a landmark randomized trial that included 7,020 patients with type 2 diabetes and established ischemic cardiovascular disease in which the SGLT2i reduced all-cause mortality by 32%, compared with placebo over a median 3.1 years of follow-up, cardiovascular mortality by 38%, and hospitalizations for heart failure by 35% (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
The mechanism responsible for these impressive clinical benefits has been unclear. The EMPA-HEART CardioLink-6 trial was a small study – 97 randomized patients – designed to shed light on this issue. The hypothesis was that SGLT2i therapy facilitates cardiac reverse remodeling. This indeed turned out to be the case when cardiac MRI findings at baseline and after 6 months were compared by blinded evaluators.
From a baseline mean left ventricular mass indexed to body surface area of 60 g/m2, which is within normal range, left ventricular mass decreased by a mean of 4.71 g in the empagliflozin group, compared with a mere 0.39-g reduction in placebo-treated controls.
Dr. Verma underscored the importance of this result: “Left ventricular mass is a strong and independent predictor of major cardiovascular events, including cardiovascular and all-cause mortality, myocardial infarction, and heart failure. Furthermore, the magnitude of left ventricular mass regression correlates with the extent of clinical outcome benefit seen with pharmacological and device therapies.”
In a prespecified subgroup analysis stratified by baseline LV mass index, patients with a baseline value greater than 60 g/m2 experienced a much greater benefit from empagliflozin, with a mean between-group difference in LV mass index reduction of 7.26 g/m2, compared with a 0.46-g/m2 difference between the SGLT2i and placebo among those with a baseline LV mass index of 60 g/m2 or less.
Ambulatory systolic blood pressure fell from a baseline of 139 mm Hg by a mean of 7.9 mm Hg in the empagliflozin group and 0.7 mm Hg with placebo. From a baseline hematocrit of 42%, hematocrit improved by an absolute 1.91% more with empagliflozin than placebo. However, there were no significant between-group differences in the secondary cardiac MRI outcomes of change in LV end-systolic volume index, LV end-diastolic volume index, or LV ejection fraction.
Discussant Elliott M. Antman, MD, hailed EMPA-HEART CardioLink-6 as “a very important mechanistic study.”
“As I leave Chicago for home, I plan to further increase the use of SGLT2 inhibitors in my patients with type 2 diabetes, especially if they have a history of heart failure, and especially if they have coronary artery disease. I would encourage you to think about doing the same, and I would also recommend that we urge our colleagues in general medicine, endocrinology, and nephrology to consider this information as well,” said Dr. Antman, professor of medicine and associate dean for clinical and translational research at Harvard Medical School, Boston, as well as an AHA past president.
He noted that EMPA-HEART CardioLink-6 provides “biologically plausible data” to explain the mechanism for the major clinical benefits of empagliflozin earlier documented in EMPA-REG OUTCOME. The likely driver of the reduction in left ventricular mass seen in EMPA-HEART CardioLink-6 was the combination of lower systolic blood pressure and higher hematocrit.
“These surrogates suggest that our traditional concepts of afterload and preload appear to be favorably affected by SGLT2 inhibition,” according to the cardiologist.
The EMPA-HEART CardioLink-6 study was funded by Boehringer Ingelheim. Dr. Verma reported receiving research support and/or speaker payments from that pharmaceutical company and roughly a dozen others. Dr. Antman had no disclosures.
SOURCE: Verma S. AHA 2018, Abstract 19332.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: .
Major finding: Six months of empagliflozin reduced left ventricular mass by a mean of 4.71 g, vs. 0.39 g with placebo.
Study details: This 97-patient, 6-month, randomized trial evaluated the impact of SGLT2 inhibition with empagliflozin on left ventricular remodeling.
Disclosures: The EMPA-HEART CardioLink-6 study was funded by Boehringer Ingelheim. The presenter reported receiving research support and/or speaker payments from that pharmaceutical company and roughly a dozen others. Source: Verma S. AHA 2018, Abstract 19332.