SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

The Food and Drug Administration has approved a transdermal asenapine delivery system (Secuado) for treatment of schizophrenia in adults, according to a release from Noven Pharmaceuticals.

Olivier Le Moal/Getty Images

The patch formulation is designed to deliver sustained concentrations of asenapine over 24-hour periods, so the system is a once-daily treatment. The efficacy and safety profile for children younger than 18 years is unknown.

The approval is based on an international, phase 3, double-blind, placebo-controlled study that included 616 adults with schizophrenia. The transdermal system achieved the study’s primary endpoint of statistically significant improvement at week 6 in the Positive and Negative Syndrome Scale, compared with placebo.

The safety profile of the system was consistent with the known profile of sublingual asenapine, and the most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain. The full prescribing information includes a boxed warning explaining that antipsychotics, such as asenapine, are associated with increased risk of death among elderly patients with dementia-related psychosis, an indication not approved for this transdermal asenapine-delivery system. Other warnings described in the prescribing information include neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes.

“In addition to offering a new delivery option, transdermal patches can also provide caretakers and health care providers with a nonintrustive, visual confirmation that a treatment is being utilized,” noted Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, in the release.

Noven is a subsidiary of Hisamitsu Pharmaceutical.

[email protected]

The Food and Drug Administration has approved a transdermal asenapine delivery system (Secuado) for treatment of schizophrenia in adults, according to a release from Noven Pharmaceuticals.

Olivier Le Moal/Getty Images

The patch formulation is designed to deliver sustained concentrations of asenapine over 24-hour periods, so the system is a once-daily treatment. The efficacy and safety profile for children younger than 18 years is unknown.

The approval is based on an international, phase 3, double-blind, placebo-controlled study that included 616 adults with schizophrenia. The transdermal system achieved the study’s primary endpoint of statistically significant improvement at week 6 in the Positive and Negative Syndrome Scale, compared with placebo.

The safety profile of the system was consistent with the known profile of sublingual asenapine, and the most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain. The full prescribing information includes a boxed warning explaining that antipsychotics, such as asenapine, are associated with increased risk of death among elderly patients with dementia-related psychosis, an indication not approved for this transdermal asenapine-delivery system. Other warnings described in the prescribing information include neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes.

“In addition to offering a new delivery option, transdermal patches can also provide caretakers and health care providers with a nonintrustive, visual confirmation that a treatment is being utilized,” noted Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, in the release.

Noven is a subsidiary of Hisamitsu Pharmaceutical.

[email protected]

The Food and Drug Administration has approved a transdermal asenapine delivery system (Secuado) for treatment of schizophrenia in adults, according to a release from Noven Pharmaceuticals.

Olivier Le Moal/Getty Images

The patch formulation is designed to deliver sustained concentrations of asenapine over 24-hour periods, so the system is a once-daily treatment. The efficacy and safety profile for children younger than 18 years is unknown.

The approval is based on an international, phase 3, double-blind, placebo-controlled study that included 616 adults with schizophrenia. The transdermal system achieved the study’s primary endpoint of statistically significant improvement at week 6 in the Positive and Negative Syndrome Scale, compared with placebo.

The safety profile of the system was consistent with the known profile of sublingual asenapine, and the most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain. The full prescribing information includes a boxed warning explaining that antipsychotics, such as asenapine, are associated with increased risk of death among elderly patients with dementia-related psychosis, an indication not approved for this transdermal asenapine-delivery system. Other warnings described in the prescribing information include neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes.

“In addition to offering a new delivery option, transdermal patches can also provide caretakers and health care providers with a nonintrustive, visual confirmation that a treatment is being utilized,” noted Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, in the release.

Noven is a subsidiary of Hisamitsu Pharmaceutical.

[email protected]

Individuals with schizophrenia had elevated levels of one Epstein-Barr virus (EBV) antibody but atypically low levels of another, which investigators deemed an “aberrant immune response.”

Faith Dickerson, PhD, MPH, Lorraine Jones-Brando, PhD,and colleagues investigated the IgG antibodies and genetics of 432 individuals with schizophrenia and 311 without. The investigators used solid-phase immunoassays to measure antibodies, and they measured titers of antibodies not just for EBV but also for related viruses. The group with schizophrenia was slightly older, with a mean age of 38.2 years, compared with a mean age of 32.03 years in the group without schizophrenia. Also, 65.7% of the study participants in the schizophrenia group were male, compared with 39.2% of those in the group without schizophrenia. More than 60% of participants in the schizophrenia group were cigarette smokers, compared with 14.8% of the controls. The study was published in Schizophrenia Bulletin.

Compared with the controls, individuals with schizophrenia had elevated levels of EBV viral capsid antibody (EBV-VCA) with a mean effect size of 0.356 (P less than .002); however, the levels of EBV nuclear antigen-1 (EBNA-1) were not significantly different from those seen in individuals without schizophrenia, reported Dr. Dickerson of the Stanley Research Program at Sheppard Pratt, and Dr. Jones-Brando of Johns Hopkins University, both in Baltimore.

The investigators also examined adjusted odds ratios for individuals with schizophrenia having levels of antibodies higher than percentile cutoffs of the controls; for example, the aOR for those individuals having EBV VCA levels at the 90th percentile of controls was 2.03 (95% confidence interval, 1.23-3.37; P = .007). The aORs for EBNA-1 were not significant.

Those results suggest an aberrant immune response to EBV because, in most cases, EBV VCA and EBNA-1 are expressed at roughly equal levels, the investigators said.

“There are a number of therapeutic interventions available for the modulation of EBV infection including antiviral medications and pharmacological compounds which can modulate the immune response,” they wrote.

“An increased understanding of the role of EBV infection might thus lead to novel methods for the prevention and treatment of schizophrenia.”

The study was funded by the Silvio O. Conte Center at Johns Hopkins University in Baltimore, and the Stanley Medical Research Institute, Chevy Chase, Md. Dr. Dickerson, Dr. Jones-Brando, and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: Dickerson F et al. Schizophr Bull. 2019 Sep 11;45(5):1112-9.

Individuals with schizophrenia had elevated levels of one Epstein-Barr virus (EBV) antibody but atypically low levels of another, which investigators deemed an “aberrant immune response.”

Faith Dickerson, PhD, MPH, Lorraine Jones-Brando, PhD,and colleagues investigated the IgG antibodies and genetics of 432 individuals with schizophrenia and 311 without. The investigators used solid-phase immunoassays to measure antibodies, and they measured titers of antibodies not just for EBV but also for related viruses. The group with schizophrenia was slightly older, with a mean age of 38.2 years, compared with a mean age of 32.03 years in the group without schizophrenia. Also, 65.7% of the study participants in the schizophrenia group were male, compared with 39.2% of those in the group without schizophrenia. More than 60% of participants in the schizophrenia group were cigarette smokers, compared with 14.8% of the controls. The study was published in Schizophrenia Bulletin.

Compared with the controls, individuals with schizophrenia had elevated levels of EBV viral capsid antibody (EBV-VCA) with a mean effect size of 0.356 (P less than .002); however, the levels of EBV nuclear antigen-1 (EBNA-1) were not significantly different from those seen in individuals without schizophrenia, reported Dr. Dickerson of the Stanley Research Program at Sheppard Pratt, and Dr. Jones-Brando of Johns Hopkins University, both in Baltimore.

The investigators also examined adjusted odds ratios for individuals with schizophrenia having levels of antibodies higher than percentile cutoffs of the controls; for example, the aOR for those individuals having EBV VCA levels at the 90th percentile of controls was 2.03 (95% confidence interval, 1.23-3.37; P = .007). The aORs for EBNA-1 were not significant.

Those results suggest an aberrant immune response to EBV because, in most cases, EBV VCA and EBNA-1 are expressed at roughly equal levels, the investigators said.

“There are a number of therapeutic interventions available for the modulation of EBV infection including antiviral medications and pharmacological compounds which can modulate the immune response,” they wrote.

“An increased understanding of the role of EBV infection might thus lead to novel methods for the prevention and treatment of schizophrenia.”

The study was funded by the Silvio O. Conte Center at Johns Hopkins University in Baltimore, and the Stanley Medical Research Institute, Chevy Chase, Md. Dr. Dickerson, Dr. Jones-Brando, and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: Dickerson F et al. Schizophr Bull. 2019 Sep 11;45(5):1112-9.

Individuals with schizophrenia had elevated levels of one Epstein-Barr virus (EBV) antibody but atypically low levels of another, which investigators deemed an “aberrant immune response.”

Faith Dickerson, PhD, MPH, Lorraine Jones-Brando, PhD,and colleagues investigated the IgG antibodies and genetics of 432 individuals with schizophrenia and 311 without. The investigators used solid-phase immunoassays to measure antibodies, and they measured titers of antibodies not just for EBV but also for related viruses. The group with schizophrenia was slightly older, with a mean age of 38.2 years, compared with a mean age of 32.03 years in the group without schizophrenia. Also, 65.7% of the study participants in the schizophrenia group were male, compared with 39.2% of those in the group without schizophrenia. More than 60% of participants in the schizophrenia group were cigarette smokers, compared with 14.8% of the controls. The study was published in Schizophrenia Bulletin.

Compared with the controls, individuals with schizophrenia had elevated levels of EBV viral capsid antibody (EBV-VCA) with a mean effect size of 0.356 (P less than .002); however, the levels of EBV nuclear antigen-1 (EBNA-1) were not significantly different from those seen in individuals without schizophrenia, reported Dr. Dickerson of the Stanley Research Program at Sheppard Pratt, and Dr. Jones-Brando of Johns Hopkins University, both in Baltimore.

The investigators also examined adjusted odds ratios for individuals with schizophrenia having levels of antibodies higher than percentile cutoffs of the controls; for example, the aOR for those individuals having EBV VCA levels at the 90th percentile of controls was 2.03 (95% confidence interval, 1.23-3.37; P = .007). The aORs for EBNA-1 were not significant.

Those results suggest an aberrant immune response to EBV because, in most cases, EBV VCA and EBNA-1 are expressed at roughly equal levels, the investigators said.

“There are a number of therapeutic interventions available for the modulation of EBV infection including antiviral medications and pharmacological compounds which can modulate the immune response,” they wrote.

“An increased understanding of the role of EBV infection might thus lead to novel methods for the prevention and treatment of schizophrenia.”

The study was funded by the Silvio O. Conte Center at Johns Hopkins University in Baltimore, and the Stanley Medical Research Institute, Chevy Chase, Md. Dr. Dickerson, Dr. Jones-Brando, and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: Dickerson F et al. Schizophr Bull. 2019 Sep 11;45(5):1112-9.

SAN DIEGO – Its toll is obscured by the opioid crisis, but methamphetamine use is on the rise in the United States. There are no approved treatments for methamphetamine use, but a psychiatrist told colleagues that several off-label medications might prove helpful.

However, the evidence supporting the use of these medications for patients taking methamphetamine is not robust, “and none are even close to [Food and Drug Administration] approval,” said Larissa J. Mooney, MD, of the University of California, Los Angeles, and the VA Greater Los Angeles Healthcare System. “But if I use something that’s approved for depression or might be helpful for anxiety symptoms, maybe it would also help reduce their likelihood of relapse in conjunction with an evidence-based behavioral program or treatment with a therapist.”

Dr. Mooney, who spoke at the annual Psych Congress, highlighted a federal report estimating that 0.4% of people aged 18-25 in 2017 used the drug within the past month, compared with 0.3% of those aged 26 and higher.

There were about 758,000 current adult users of methamphetamine in 2017, the report found.

Meanwhile, concurrent use of methamphetamine among patients who use opioids chronically has almost doubled, to 34% in 2017, from 19% in 2011 (Drug Alcohol Depend. 2018 Dec 1;193:14-20). And, Dr. Mooney said, deaths from stimulants are rising, even independent of opioid deaths.

Stimulant users typically have other psychiatric conditions, such as depression, anxiety, and concentration problems, Dr. Mooney said. In those cases, she said, treating those conditions might help with the substance use, too.

For methamphetamine use disorder, she highlighted some medications that might be helpful, although, again, she cautioned that evidence is not strong:

• Bupropion (Wellbutrin). Research suggests that this drug is more effective in patients with less severe methamphetamine use disorder, Dr. Mooney said. “It’s a more stimulating antidepressant, and can be helpful with concentration and attention.”
• Mirtazapine (Remeron). “I keep it in my list of options for some [who are] really anxious and not sleeping well,” she said. “It might be beneficial.”
• Naltrexone (ReVia, Depade, Vivitrol). “There are some early signs of efficacy,” she said, and a randomized, controlled trial is in progress.
• Methylphenidate (Ritalin, Concerta) and topiramate (Topamax). There’s “low-strength” evidence that the drugs can be helpful and lower use of methamphetamine, she said. However, methylphenidate is a stimulant. There’s controversy over the use of stimulants to treat patients with substance use disorders, Dr. Mooney said, and she tends to be conservative about their use in this population.

Why not use them to treat methamphetamine users in the same way that opioids such as methadone are used to treat opioid use addiction? “We don’t have an equivalent stimulant that works in the same way,” she said. “They don’t stay in the system for 24 hours. If you take a prescription stimulant, by the end of the day it wears off. It won’t stay in the same way as agonist treatments for opioid disorder.”

Even so, she said, “it makes sense that stimulants might be helpful.”

Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.

SAN DIEGO – Its toll is obscured by the opioid crisis, but methamphetamine use is on the rise in the United States. There are no approved treatments for methamphetamine use, but a psychiatrist told colleagues that several off-label medications might prove helpful.

However, the evidence supporting the use of these medications for patients taking methamphetamine is not robust, “and none are even close to [Food and Drug Administration] approval,” said Larissa J. Mooney, MD, of the University of California, Los Angeles, and the VA Greater Los Angeles Healthcare System. “But if I use something that’s approved for depression or might be helpful for anxiety symptoms, maybe it would also help reduce their likelihood of relapse in conjunction with an evidence-based behavioral program or treatment with a therapist.”

Dr. Mooney, who spoke at the annual Psych Congress, highlighted a federal report estimating that 0.4% of people aged 18-25 in 2017 used the drug within the past month, compared with 0.3% of those aged 26 and higher.

There were about 758,000 current adult users of methamphetamine in 2017, the report found.

Meanwhile, concurrent use of methamphetamine among patients who use opioids chronically has almost doubled, to 34% in 2017, from 19% in 2011 (Drug Alcohol Depend. 2018 Dec 1;193:14-20). And, Dr. Mooney said, deaths from stimulants are rising, even independent of opioid deaths.

Stimulant users typically have other psychiatric conditions, such as depression, anxiety, and concentration problems, Dr. Mooney said. In those cases, she said, treating those conditions might help with the substance use, too.

For methamphetamine use disorder, she highlighted some medications that might be helpful, although, again, she cautioned that evidence is not strong:

• Bupropion (Wellbutrin). Research suggests that this drug is more effective in patients with less severe methamphetamine use disorder, Dr. Mooney said. “It’s a more stimulating antidepressant, and can be helpful with concentration and attention.”
• Mirtazapine (Remeron). “I keep it in my list of options for some [who are] really anxious and not sleeping well,” she said. “It might be beneficial.”
• Naltrexone (ReVia, Depade, Vivitrol). “There are some early signs of efficacy,” she said, and a randomized, controlled trial is in progress.
• Methylphenidate (Ritalin, Concerta) and topiramate (Topamax). There’s “low-strength” evidence that the drugs can be helpful and lower use of methamphetamine, she said. However, methylphenidate is a stimulant. There’s controversy over the use of stimulants to treat patients with substance use disorders, Dr. Mooney said, and she tends to be conservative about their use in this population.

Why not use them to treat methamphetamine users in the same way that opioids such as methadone are used to treat opioid use addiction? “We don’t have an equivalent stimulant that works in the same way,” she said. “They don’t stay in the system for 24 hours. If you take a prescription stimulant, by the end of the day it wears off. It won’t stay in the same way as agonist treatments for opioid disorder.”

Even so, she said, “it makes sense that stimulants might be helpful.”

Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.

SAN DIEGO – Its toll is obscured by the opioid crisis, but methamphetamine use is on the rise in the United States. There are no approved treatments for methamphetamine use, but a psychiatrist told colleagues that several off-label medications might prove helpful.

However, the evidence supporting the use of these medications for patients taking methamphetamine is not robust, “and none are even close to [Food and Drug Administration] approval,” said Larissa J. Mooney, MD, of the University of California, Los Angeles, and the VA Greater Los Angeles Healthcare System. “But if I use something that’s approved for depression or might be helpful for anxiety symptoms, maybe it would also help reduce their likelihood of relapse in conjunction with an evidence-based behavioral program or treatment with a therapist.”

Dr. Mooney, who spoke at the annual Psych Congress, highlighted a federal report estimating that 0.4% of people aged 18-25 in 2017 used the drug within the past month, compared with 0.3% of those aged 26 and higher.

There were about 758,000 current adult users of methamphetamine in 2017, the report found.

Meanwhile, concurrent use of methamphetamine among patients who use opioids chronically has almost doubled, to 34% in 2017, from 19% in 2011 (Drug Alcohol Depend. 2018 Dec 1;193:14-20). And, Dr. Mooney said, deaths from stimulants are rising, even independent of opioid deaths.

Stimulant users typically have other psychiatric conditions, such as depression, anxiety, and concentration problems, Dr. Mooney said. In those cases, she said, treating those conditions might help with the substance use, too.

For methamphetamine use disorder, she highlighted some medications that might be helpful, although, again, she cautioned that evidence is not strong:

• Bupropion (Wellbutrin). Research suggests that this drug is more effective in patients with less severe methamphetamine use disorder, Dr. Mooney said. “It’s a more stimulating antidepressant, and can be helpful with concentration and attention.”
• Mirtazapine (Remeron). “I keep it in my list of options for some [who are] really anxious and not sleeping well,” she said. “It might be beneficial.”
• Naltrexone (ReVia, Depade, Vivitrol). “There are some early signs of efficacy,” she said, and a randomized, controlled trial is in progress.
• Methylphenidate (Ritalin, Concerta) and topiramate (Topamax). There’s “low-strength” evidence that the drugs can be helpful and lower use of methamphetamine, she said. However, methylphenidate is a stimulant. There’s controversy over the use of stimulants to treat patients with substance use disorders, Dr. Mooney said, and she tends to be conservative about their use in this population.

Why not use them to treat methamphetamine users in the same way that opioids such as methadone are used to treat opioid use addiction? “We don’t have an equivalent stimulant that works in the same way,” she said. “They don’t stay in the system for 24 hours. If you take a prescription stimulant, by the end of the day it wears off. It won’t stay in the same way as agonist treatments for opioid disorder.”

Even so, she said, “it makes sense that stimulants might be helpful.”

Dr. Mooney disclosed an advisory board relationship with Alkermes and grant/research support from the National Institute on Drug Abuse.

Maternal weight gains at either end of the weight spectrum may influence the risk of poor neonatal outcomes for twins, Lisa M. Bodnar, PhD, and colleagues determined.

anopdesignstock/Thinkstock

The risks of cesarean section and neonatal death were elevated for those mothers who were overweight before pregnancy and then gained too much. But infants of underweight women who didn’t gain enough faced risks as well, wrote Dr. Bodnar of the University of Pittsburgh and associates in Obstetrics & Gynecology.

Among the most severely overweight women (obesity grade 2 or 3) who gained the most weight (43 kg) at 37 weeks’ gestation, there were 6 fewer small-for-gestational-age (SGA) infants per 100 births, but 14 more large-for-gestational-age (LGA) infants, 4 more cesarean deliveries, and 2 more neonatal deaths per 100 births. By contrast, among the most severely underweight women who gained the least amount of weight (9 kg), there were 18 more SGA infants, 3 fewer LGA infants, and 11 fewer cesareans, but 6 more preterm births before 32 weeks’ gestation.

The same U-shaped pattern also occurred within the individual weight categories. For example, compared with the outcomes among the most underweight women who gained least, among underweight women who gained the most (37 kg), there were eight fewer SGA infants, but four more LGA infants, 16 excess preterm births, and 9 excess infant deaths.

“If the associations we observed are even partially reflective of causality, targeted modification of pregnancy weight gain in women carrying twins might improve pregnancy outcomes,” wrote Dr. Bodnar and her team. “Data on a wide range of short- and long-term outcomes and information on the relative seriousness of these outcomes are needed to determine optimal gestational weight gain ranges for twin pregnancies.”

The cohort comprised 54,836 live-born twins from 27,723 twin pregnancies who were included in the MOMs database maintained by the University of Pennsylvania, Philadelphia. The population-based study tracks maternal obesity, gestational weight gain, and adverse birth outcomes. The information came from infant birth and death vital statistics records from 2003 to 2013.

However, this very source puts the findings in some degree of uncertainty, Ozhan Turan, MD, said in an interview.

“It’s a very nice study, and the statistics are very well done,” said Dr. Turan, who is the director of fetal therapy and complex obstetric surgery at the University of Maryland School of Medicine. “But that kind of data has pitfalls that are unavoidable. For example, they don’t have access to maternal medical comorbidities which are mostly related to the outcome, particularly gestational diabetes and preeclampsia. They also don’t have the information on chorionicity – and we know that monochorionic twins face much greater risk for these outcomes than dichorionic twins.”

The investigators calculated total gestational weight gain by subtracting prepregnancy weight from maternal weight at delivery. The analysis controlled for race and ethnicity, education, neonatal care, level of birth facility, parity, payment at delivery, smoking during pregnancy, marital status, year of birth, height, maternal age, preexisting diabetes or hypertension, infertility treatment, neonatal sex, and racial composition of neighborhood, as a proxy of neighborhood-level socioeconomic status. Approximately 16% of mothers received infertility treatment.

Of the cohort, 3% were underweight, 48% were normal weight, 24% were overweight, 13% were grade 1 obese, 7% grade 2 obese, and 5% grade 3 obese.

“Pregnancy weight gain was negatively associated with SGA and positively associated with LGA and cesarean delivery in all [body mass index] groups. For example, among normal-weight women, compared with a pregnancy weight gain equivalent to 20 kg at 37 weeks’ of gestation, a weight gain of 27 kg at 37 weeks’ of gestation was associated with 2.2 fewer cases of SGA but 2.9 more cases of LGA and 3.7 more cases of cesarean delivery,” Dr. Bodnar and associates wrote.

The investigators found that “weight gains well above or well below the [Institute of Medicine] provisional guidelines (less than 14 kg or more than 27 kg in underweight or normal-weight women, less than 11 kg or more than 28 kg in overweight women, and less than 6.4 kg or more than 26 kg in women with obesity) were associated with the highest risk of adverse outcomes.”

“I would not say this is practice-changing information,” said Dr. Turan. “We already know all this. What would be very helpful is an algorithm to tell us, if a patient is pregnant with twins, this is the amount of weight you have to gain.”

For overweight patients, Dr. Turan tries to impart the key message of moderate or slight weight gain, according to prepregnancy body mass index. For underweight patients, the picture is a bit more complex.

“There are not that many who are underweight before pregnancy, so first thing I look for is the reason a woman is underweight. Is she just not eating properly? Is there a drug dependence issue, alcohol dependence, HIV? Is there smoking? A gut problem that causes malnutrition. You can’t just say ‘eat more.’ That does not solve the problem. We need to find out why she is underweight and fix that first,” said Dr. Turan.

Neither Dr. Bodnar nor Dr. Turan had any relevant financial disclosures. One coauthor disclosed her institution received funds from the University of Pittsburgh. The study was funded by National Institutes of Health grants.
 

SOURCE: Bodnar LM et al. Obstet Gynecol. 2019;134:1075-86.

Maternal weight gains at either end of the weight spectrum may influence the risk of poor neonatal outcomes for twins, Lisa M. Bodnar, PhD, and colleagues determined.

anopdesignstock/Thinkstock

The risks of cesarean section and neonatal death were elevated for those mothers who were overweight before pregnancy and then gained too much. But infants of underweight women who didn’t gain enough faced risks as well, wrote Dr. Bodnar of the University of Pittsburgh and associates in Obstetrics & Gynecology.

Among the most severely overweight women (obesity grade 2 or 3) who gained the most weight (43 kg) at 37 weeks’ gestation, there were 6 fewer small-for-gestational-age (SGA) infants per 100 births, but 14 more large-for-gestational-age (LGA) infants, 4 more cesarean deliveries, and 2 more neonatal deaths per 100 births. By contrast, among the most severely underweight women who gained the least amount of weight (9 kg), there were 18 more SGA infants, 3 fewer LGA infants, and 11 fewer cesareans, but 6 more preterm births before 32 weeks’ gestation.

The same U-shaped pattern also occurred within the individual weight categories. For example, compared with the outcomes among the most underweight women who gained least, among underweight women who gained the most (37 kg), there were eight fewer SGA infants, but four more LGA infants, 16 excess preterm births, and 9 excess infant deaths.

“If the associations we observed are even partially reflective of causality, targeted modification of pregnancy weight gain in women carrying twins might improve pregnancy outcomes,” wrote Dr. Bodnar and her team. “Data on a wide range of short- and long-term outcomes and information on the relative seriousness of these outcomes are needed to determine optimal gestational weight gain ranges for twin pregnancies.”

The cohort comprised 54,836 live-born twins from 27,723 twin pregnancies who were included in the MOMs database maintained by the University of Pennsylvania, Philadelphia. The population-based study tracks maternal obesity, gestational weight gain, and adverse birth outcomes. The information came from infant birth and death vital statistics records from 2003 to 2013.

However, this very source puts the findings in some degree of uncertainty, Ozhan Turan, MD, said in an interview.

“It’s a very nice study, and the statistics are very well done,” said Dr. Turan, who is the director of fetal therapy and complex obstetric surgery at the University of Maryland School of Medicine. “But that kind of data has pitfalls that are unavoidable. For example, they don’t have access to maternal medical comorbidities which are mostly related to the outcome, particularly gestational diabetes and preeclampsia. They also don’t have the information on chorionicity – and we know that monochorionic twins face much greater risk for these outcomes than dichorionic twins.”

The investigators calculated total gestational weight gain by subtracting prepregnancy weight from maternal weight at delivery. The analysis controlled for race and ethnicity, education, neonatal care, level of birth facility, parity, payment at delivery, smoking during pregnancy, marital status, year of birth, height, maternal age, preexisting diabetes or hypertension, infertility treatment, neonatal sex, and racial composition of neighborhood, as a proxy of neighborhood-level socioeconomic status. Approximately 16% of mothers received infertility treatment.

Of the cohort, 3% were underweight, 48% were normal weight, 24% were overweight, 13% were grade 1 obese, 7% grade 2 obese, and 5% grade 3 obese.

“Pregnancy weight gain was negatively associated with SGA and positively associated with LGA and cesarean delivery in all [body mass index] groups. For example, among normal-weight women, compared with a pregnancy weight gain equivalent to 20 kg at 37 weeks’ of gestation, a weight gain of 27 kg at 37 weeks’ of gestation was associated with 2.2 fewer cases of SGA but 2.9 more cases of LGA and 3.7 more cases of cesarean delivery,” Dr. Bodnar and associates wrote.

The investigators found that “weight gains well above or well below the [Institute of Medicine] provisional guidelines (less than 14 kg or more than 27 kg in underweight or normal-weight women, less than 11 kg or more than 28 kg in overweight women, and less than 6.4 kg or more than 26 kg in women with obesity) were associated with the highest risk of adverse outcomes.”

“I would not say this is practice-changing information,” said Dr. Turan. “We already know all this. What would be very helpful is an algorithm to tell us, if a patient is pregnant with twins, this is the amount of weight you have to gain.”

For overweight patients, Dr. Turan tries to impart the key message of moderate or slight weight gain, according to prepregnancy body mass index. For underweight patients, the picture is a bit more complex.

“There are not that many who are underweight before pregnancy, so first thing I look for is the reason a woman is underweight. Is she just not eating properly? Is there a drug dependence issue, alcohol dependence, HIV? Is there smoking? A gut problem that causes malnutrition. You can’t just say ‘eat more.’ That does not solve the problem. We need to find out why she is underweight and fix that first,” said Dr. Turan.

Neither Dr. Bodnar nor Dr. Turan had any relevant financial disclosures. One coauthor disclosed her institution received funds from the University of Pittsburgh. The study was funded by National Institutes of Health grants.
 

SOURCE: Bodnar LM et al. Obstet Gynecol. 2019;134:1075-86.

Maternal weight gains at either end of the weight spectrum may influence the risk of poor neonatal outcomes for twins, Lisa M. Bodnar, PhD, and colleagues determined.

anopdesignstock/Thinkstock

The risks of cesarean section and neonatal death were elevated for those mothers who were overweight before pregnancy and then gained too much. But infants of underweight women who didn’t gain enough faced risks as well, wrote Dr. Bodnar of the University of Pittsburgh and associates in Obstetrics & Gynecology.

Among the most severely overweight women (obesity grade 2 or 3) who gained the most weight (43 kg) at 37 weeks’ gestation, there were 6 fewer small-for-gestational-age (SGA) infants per 100 births, but 14 more large-for-gestational-age (LGA) infants, 4 more cesarean deliveries, and 2 more neonatal deaths per 100 births. By contrast, among the most severely underweight women who gained the least amount of weight (9 kg), there were 18 more SGA infants, 3 fewer LGA infants, and 11 fewer cesareans, but 6 more preterm births before 32 weeks’ gestation.

The same U-shaped pattern also occurred within the individual weight categories. For example, compared with the outcomes among the most underweight women who gained least, among underweight women who gained the most (37 kg), there were eight fewer SGA infants, but four more LGA infants, 16 excess preterm births, and 9 excess infant deaths.

“If the associations we observed are even partially reflective of causality, targeted modification of pregnancy weight gain in women carrying twins might improve pregnancy outcomes,” wrote Dr. Bodnar and her team. “Data on a wide range of short- and long-term outcomes and information on the relative seriousness of these outcomes are needed to determine optimal gestational weight gain ranges for twin pregnancies.”

The cohort comprised 54,836 live-born twins from 27,723 twin pregnancies who were included in the MOMs database maintained by the University of Pennsylvania, Philadelphia. The population-based study tracks maternal obesity, gestational weight gain, and adverse birth outcomes. The information came from infant birth and death vital statistics records from 2003 to 2013.

However, this very source puts the findings in some degree of uncertainty, Ozhan Turan, MD, said in an interview.

“It’s a very nice study, and the statistics are very well done,” said Dr. Turan, who is the director of fetal therapy and complex obstetric surgery at the University of Maryland School of Medicine. “But that kind of data has pitfalls that are unavoidable. For example, they don’t have access to maternal medical comorbidities which are mostly related to the outcome, particularly gestational diabetes and preeclampsia. They also don’t have the information on chorionicity – and we know that monochorionic twins face much greater risk for these outcomes than dichorionic twins.”

The investigators calculated total gestational weight gain by subtracting prepregnancy weight from maternal weight at delivery. The analysis controlled for race and ethnicity, education, neonatal care, level of birth facility, parity, payment at delivery, smoking during pregnancy, marital status, year of birth, height, maternal age, preexisting diabetes or hypertension, infertility treatment, neonatal sex, and racial composition of neighborhood, as a proxy of neighborhood-level socioeconomic status. Approximately 16% of mothers received infertility treatment.

Of the cohort, 3% were underweight, 48% were normal weight, 24% were overweight, 13% were grade 1 obese, 7% grade 2 obese, and 5% grade 3 obese.

“Pregnancy weight gain was negatively associated with SGA and positively associated with LGA and cesarean delivery in all [body mass index] groups. For example, among normal-weight women, compared with a pregnancy weight gain equivalent to 20 kg at 37 weeks’ of gestation, a weight gain of 27 kg at 37 weeks’ of gestation was associated with 2.2 fewer cases of SGA but 2.9 more cases of LGA and 3.7 more cases of cesarean delivery,” Dr. Bodnar and associates wrote.

The investigators found that “weight gains well above or well below the [Institute of Medicine] provisional guidelines (less than 14 kg or more than 27 kg in underweight or normal-weight women, less than 11 kg or more than 28 kg in overweight women, and less than 6.4 kg or more than 26 kg in women with obesity) were associated with the highest risk of adverse outcomes.”

“I would not say this is practice-changing information,” said Dr. Turan. “We already know all this. What would be very helpful is an algorithm to tell us, if a patient is pregnant with twins, this is the amount of weight you have to gain.”

For overweight patients, Dr. Turan tries to impart the key message of moderate or slight weight gain, according to prepregnancy body mass index. For underweight patients, the picture is a bit more complex.

“There are not that many who are underweight before pregnancy, so first thing I look for is the reason a woman is underweight. Is she just not eating properly? Is there a drug dependence issue, alcohol dependence, HIV? Is there smoking? A gut problem that causes malnutrition. You can’t just say ‘eat more.’ That does not solve the problem. We need to find out why she is underweight and fix that first,” said Dr. Turan.

Neither Dr. Bodnar nor Dr. Turan had any relevant financial disclosures. One coauthor disclosed her institution received funds from the University of Pittsburgh. The study was funded by National Institutes of Health grants.
 

SOURCE: Bodnar LM et al. Obstet Gynecol. 2019;134:1075-86.

PARIS – A practical strategy of early and aggressive vasodilation and optimization of long-term medication for acute heart failure did not budge all-cause mortality or 180-day readmission rates, according to results of a pragmatic trial presented at the annual congress of the European Society of Cardiology.

“To our great disappointment, the curves were superimposable” between intervention and control arms in the GALACTIC (Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation) trial, said lead investigator Christian Eugen Mueller, MD. “There was no signal of a benefit” for those receiving the targeted intervention: the adjusted hazard ratio was 1.07 for the composite primary endpoint of all-cause mortality or 6-month readmission for acute heart failure (P = 0.59).

GALACTIC, explained Dr. Mueller, was the largest investigator-initiated, randomized, controlled trial of pharmacologic therapy for acute heart failure (AHF).

“It is different in that it did not investigate a single drug, but a strategy of early, intensive, and sustained vasodilation. It is also unique in that it used individual doses of well-characterized, widely available, and mostly inexpensive drugs,” said Dr. Mueller, director of the Cardiovascular Research Institute at the University Hospital, Basel, Switzerland. “So this would have the beauty that, if it has a positive finding, you – in whatever country you come from – would be immediately able to apply it once you’re back home in your institution.”

The study attempted to address the gap between symptom amelioration and long-term outcomes when patients arrive in the ED with AHF. “Despite symptomatic improvement achieved from loop diuretics, mortality and morbidity remain unacceptably high,” said Dr. Mueller, with 40%-50% of AHF patients experiencing rehospitalization or death within 180 days of discharge.

Much remains unknown about the optimal treatment strategy for AHF. Aggressive vasodilation has been shown to improve outcomes in less-severe AHF, and intravenous nitrates are known to improve outcomes in AHF where severe pulmonary edema is present – “a phenotype representing only about 5% of patients,” noted Dr. Mueller. Still, “it is unknown whether aggressive vasodilation also improves outcomes in the much more common less-severe phenotype.”

Also, previous trials that ran intravenous vasodilators at a fixed dose for 48 hours did not improve AHF outcomes, so a one-size-fits-all strategy was not one the GALACTIC investigators sought to pursue.

In addition to a flexible regimen, “any strategy applied needs to take into consideration that the vast majority of patients with acute heart failure, after initial treatment in the ED, are then treated in a general cardiology ward,” added Dr. Mueller.

This meant that intravenous nitrate infusion was not part of the GALACTIC trial; rather, sublingual and transdermal nitrates were used, explained Dr. Mueller. “Transdermal application has the beauty that if you have an adverse effect – and hypotension is the most dangerous one – you can immediately remove the patch, and thereby avoid any further harm.”

The two-part strategy tested in GALACTIC involved reducing cardiac filling pressures by maintaining or increasing organ perfusion, while also increasing “long-term lifesaving therapy” targeting the renin-angiotensin-aldosterone system during hospitalization, with a goal to continue optimal treatment long term.

ACE inhibitors or angiotensin receptor blockers were added on the second day of hospitalization for the intervention group, said Dr. Mueller, and “in the ideal setting, up-titrated very aggressively from day to day.

“However, as you know, up-titration to target dose is sometimes wishful thinking in this frail population,” he said, so the GALACTIC trial protocol included a scheme to back dosing off for hypotension, hypokalemia, or worsening renal function. Systolic BP guided how aggressively vasodilation and ACE inhibitor/angiotensin receptor blocker therapy were escalated.

In the end, 382 patients randomized to the intervention arm received early, intensive, and sustained vasodilation, and the 399 patients in the control arm received standard-of-care treatment according to ESC guidelines. These figures omit two patients in the standard-of-care arm who withdrew consent, but follow-up was otherwise complete, said Dr. Mueller. Physicians treating patients in both study arms had discretion to use such other therapies as loop diuretics, beta-blockers, aldosterone antagonists, and cardiac devices.

Adult patients coming to the ED with acute dyspnea classified as New York Heart Association class III or IV were eligible if they had brain natriuretic peptide (BNP) levels of at least 500 ng/L, or N-terminal of the prohormone BNP (NT-proBNP) levels of at least 2,000 ng/L.

Overall, patients enrolled in GALACTIC were in their late 70s, and women made up 37% of the population.

The actual median BNP for enrollees was about 1,250 ng/L, and the median NT-proBNP was just under 6,000 ng/L. The median left ventricular ejection fraction was 37%. About a third of patients had diabetes, and 85% had hypertension. Over half had known chronic heart failure, about a third had prior history of MI, and half of patients had atrial fibrillation at baseline.

“Signs of congestion were present in all patients, and over 90% had rales on physical examination,” said Dr. Mueller.

Patients who were destined for the ICU, those who had systolic BP below 100 mm Hg or marked creatinine elevation, or who required cardiopulmonary resuscitation were excluded. Also excluded were patients with known structural defects such as severe valvular stenosis, congenital heart disease, or hypertrophic obstructive cardiomyopathy. GALACTIC also excluded patients with isolated right ventricular failure caused by pulmonary hypertension.

Prespecified subgroup analyses compared women with men, and those younger than 75 years with older participants. Women saw a significantly higher hazard ratio for readmission or death, indicating a potential harm from the intervention, said Dr. Mueller. An additional analysis stratified patients by left ventricular ejection fraction. Aside from the intervention’s negative effect on women participating in the trial, no other subgroups benefited or were harmed by an early vasodilation strategy.

Alexandre Mebazaa, MD, the designated discussant for the presentation, said that, although the GALACTIC trial was neutral, it represents “an important step forward in acute heart failure.

“Congratulations: First, because we know that in the critically ill condition it’s very difficult to do trials,” and the GALACTIC investigators succeeded in enrolling patients within the first 5 hours of presentation to EDs, noted Dr. Mebazaa, professor of anesthesiology and critical care medicine at the Paris Diderot School of Medicine.

He added that GALACTIC succeeded in continuing vasodilator use beyond the 48-hour mark. “For the first time, you had the courage to go a little bit further down, and we see that patients got the drug with vasodilator properties for 2 days or more.”

However, the long recruitment period for GALACTIC – first enrollment began in 2007 – meant that the study design reflected a thought process about AHF that doesn’t necessarily reflect current practice, noted Dr. Mebazaa. “The trial was designed many years ago, and at that time, we were still thinking that giving very aggressive treatment in the first hours could have an impact.

“Now, when we will be treating patients with vasodilators with acute heart failure – at least myself and my group – I would really wonder whether there is still evidence in the world to support the use of those agents.”

Dr. Mueller noted limitations of the GALACTIC trial, including the lack of generalizability to patients with systolic hypotension or severe renal dysfunction, since these populations were excluded. Also, “the open-label design, which was mandated by the aim to test a strategy, not a single drug, may have introduced a bias in the unblinded assessment of dyspnea” during inpatient stay.

The study was funded by several Swiss research institutions and had no industry support. Dr. Mueller reported no relevant conflicts of interest. Dr. Mebazaa reported financial relationships with Roche, Service, Novartis, AstraZeneca, S-Form Pharma, 4Teen$4, Adrenomed, and Sphingotec.

[email protected]

SOURCE: Mueller C. ESC 2019, Hot Line Session 3.

PARIS – A practical strategy of early and aggressive vasodilation and optimization of long-term medication for acute heart failure did not budge all-cause mortality or 180-day readmission rates, according to results of a pragmatic trial presented at the annual congress of the European Society of Cardiology.

“To our great disappointment, the curves were superimposable” between intervention and control arms in the GALACTIC (Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation) trial, said lead investigator Christian Eugen Mueller, MD. “There was no signal of a benefit” for those receiving the targeted intervention: the adjusted hazard ratio was 1.07 for the composite primary endpoint of all-cause mortality or 6-month readmission for acute heart failure (P = 0.59).

GALACTIC, explained Dr. Mueller, was the largest investigator-initiated, randomized, controlled trial of pharmacologic therapy for acute heart failure (AHF).

“It is different in that it did not investigate a single drug, but a strategy of early, intensive, and sustained vasodilation. It is also unique in that it used individual doses of well-characterized, widely available, and mostly inexpensive drugs,” said Dr. Mueller, director of the Cardiovascular Research Institute at the University Hospital, Basel, Switzerland. “So this would have the beauty that, if it has a positive finding, you – in whatever country you come from – would be immediately able to apply it once you’re back home in your institution.”

The study attempted to address the gap between symptom amelioration and long-term outcomes when patients arrive in the ED with AHF. “Despite symptomatic improvement achieved from loop diuretics, mortality and morbidity remain unacceptably high,” said Dr. Mueller, with 40%-50% of AHF patients experiencing rehospitalization or death within 180 days of discharge.

Much remains unknown about the optimal treatment strategy for AHF. Aggressive vasodilation has been shown to improve outcomes in less-severe AHF, and intravenous nitrates are known to improve outcomes in AHF where severe pulmonary edema is present – “a phenotype representing only about 5% of patients,” noted Dr. Mueller. Still, “it is unknown whether aggressive vasodilation also improves outcomes in the much more common less-severe phenotype.”

Also, previous trials that ran intravenous vasodilators at a fixed dose for 48 hours did not improve AHF outcomes, so a one-size-fits-all strategy was not one the GALACTIC investigators sought to pursue.

In addition to a flexible regimen, “any strategy applied needs to take into consideration that the vast majority of patients with acute heart failure, after initial treatment in the ED, are then treated in a general cardiology ward,” added Dr. Mueller.

This meant that intravenous nitrate infusion was not part of the GALACTIC trial; rather, sublingual and transdermal nitrates were used, explained Dr. Mueller. “Transdermal application has the beauty that if you have an adverse effect – and hypotension is the most dangerous one – you can immediately remove the patch, and thereby avoid any further harm.”

The two-part strategy tested in GALACTIC involved reducing cardiac filling pressures by maintaining or increasing organ perfusion, while also increasing “long-term lifesaving therapy” targeting the renin-angiotensin-aldosterone system during hospitalization, with a goal to continue optimal treatment long term.

ACE inhibitors or angiotensin receptor blockers were added on the second day of hospitalization for the intervention group, said Dr. Mueller, and “in the ideal setting, up-titrated very aggressively from day to day.

“However, as you know, up-titration to target dose is sometimes wishful thinking in this frail population,” he said, so the GALACTIC trial protocol included a scheme to back dosing off for hypotension, hypokalemia, or worsening renal function. Systolic BP guided how aggressively vasodilation and ACE inhibitor/angiotensin receptor blocker therapy were escalated.

In the end, 382 patients randomized to the intervention arm received early, intensive, and sustained vasodilation, and the 399 patients in the control arm received standard-of-care treatment according to ESC guidelines. These figures omit two patients in the standard-of-care arm who withdrew consent, but follow-up was otherwise complete, said Dr. Mueller. Physicians treating patients in both study arms had discretion to use such other therapies as loop diuretics, beta-blockers, aldosterone antagonists, and cardiac devices.

Adult patients coming to the ED with acute dyspnea classified as New York Heart Association class III or IV were eligible if they had brain natriuretic peptide (BNP) levels of at least 500 ng/L, or N-terminal of the prohormone BNP (NT-proBNP) levels of at least 2,000 ng/L.

Overall, patients enrolled in GALACTIC were in their late 70s, and women made up 37% of the population.

The actual median BNP for enrollees was about 1,250 ng/L, and the median NT-proBNP was just under 6,000 ng/L. The median left ventricular ejection fraction was 37%. About a third of patients had diabetes, and 85% had hypertension. Over half had known chronic heart failure, about a third had prior history of MI, and half of patients had atrial fibrillation at baseline.

“Signs of congestion were present in all patients, and over 90% had rales on physical examination,” said Dr. Mueller.

Patients who were destined for the ICU, those who had systolic BP below 100 mm Hg or marked creatinine elevation, or who required cardiopulmonary resuscitation were excluded. Also excluded were patients with known structural defects such as severe valvular stenosis, congenital heart disease, or hypertrophic obstructive cardiomyopathy. GALACTIC also excluded patients with isolated right ventricular failure caused by pulmonary hypertension.

Prespecified subgroup analyses compared women with men, and those younger than 75 years with older participants. Women saw a significantly higher hazard ratio for readmission or death, indicating a potential harm from the intervention, said Dr. Mueller. An additional analysis stratified patients by left ventricular ejection fraction. Aside from the intervention’s negative effect on women participating in the trial, no other subgroups benefited or were harmed by an early vasodilation strategy.

Alexandre Mebazaa, MD, the designated discussant for the presentation, said that, although the GALACTIC trial was neutral, it represents “an important step forward in acute heart failure.

“Congratulations: First, because we know that in the critically ill condition it’s very difficult to do trials,” and the GALACTIC investigators succeeded in enrolling patients within the first 5 hours of presentation to EDs, noted Dr. Mebazaa, professor of anesthesiology and critical care medicine at the Paris Diderot School of Medicine.

He added that GALACTIC succeeded in continuing vasodilator use beyond the 48-hour mark. “For the first time, you had the courage to go a little bit further down, and we see that patients got the drug with vasodilator properties for 2 days or more.”

However, the long recruitment period for GALACTIC – first enrollment began in 2007 – meant that the study design reflected a thought process about AHF that doesn’t necessarily reflect current practice, noted Dr. Mebazaa. “The trial was designed many years ago, and at that time, we were still thinking that giving very aggressive treatment in the first hours could have an impact.

“Now, when we will be treating patients with vasodilators with acute heart failure – at least myself and my group – I would really wonder whether there is still evidence in the world to support the use of those agents.”

Dr. Mueller noted limitations of the GALACTIC trial, including the lack of generalizability to patients with systolic hypotension or severe renal dysfunction, since these populations were excluded. Also, “the open-label design, which was mandated by the aim to test a strategy, not a single drug, may have introduced a bias in the unblinded assessment of dyspnea” during inpatient stay.

The study was funded by several Swiss research institutions and had no industry support. Dr. Mueller reported no relevant conflicts of interest. Dr. Mebazaa reported financial relationships with Roche, Service, Novartis, AstraZeneca, S-Form Pharma, 4Teen$4, Adrenomed, and Sphingotec.

[email protected]

SOURCE: Mueller C. ESC 2019, Hot Line Session 3.

PARIS – A practical strategy of early and aggressive vasodilation and optimization of long-term medication for acute heart failure did not budge all-cause mortality or 180-day readmission rates, according to results of a pragmatic trial presented at the annual congress of the European Society of Cardiology.

“To our great disappointment, the curves were superimposable” between intervention and control arms in the GALACTIC (Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation) trial, said lead investigator Christian Eugen Mueller, MD. “There was no signal of a benefit” for those receiving the targeted intervention: the adjusted hazard ratio was 1.07 for the composite primary endpoint of all-cause mortality or 6-month readmission for acute heart failure (P = 0.59).

GALACTIC, explained Dr. Mueller, was the largest investigator-initiated, randomized, controlled trial of pharmacologic therapy for acute heart failure (AHF).

“It is different in that it did not investigate a single drug, but a strategy of early, intensive, and sustained vasodilation. It is also unique in that it used individual doses of well-characterized, widely available, and mostly inexpensive drugs,” said Dr. Mueller, director of the Cardiovascular Research Institute at the University Hospital, Basel, Switzerland. “So this would have the beauty that, if it has a positive finding, you – in whatever country you come from – would be immediately able to apply it once you’re back home in your institution.”

The study attempted to address the gap between symptom amelioration and long-term outcomes when patients arrive in the ED with AHF. “Despite symptomatic improvement achieved from loop diuretics, mortality and morbidity remain unacceptably high,” said Dr. Mueller, with 40%-50% of AHF patients experiencing rehospitalization or death within 180 days of discharge.

Much remains unknown about the optimal treatment strategy for AHF. Aggressive vasodilation has been shown to improve outcomes in less-severe AHF, and intravenous nitrates are known to improve outcomes in AHF where severe pulmonary edema is present – “a phenotype representing only about 5% of patients,” noted Dr. Mueller. Still, “it is unknown whether aggressive vasodilation also improves outcomes in the much more common less-severe phenotype.”

Also, previous trials that ran intravenous vasodilators at a fixed dose for 48 hours did not improve AHF outcomes, so a one-size-fits-all strategy was not one the GALACTIC investigators sought to pursue.

In addition to a flexible regimen, “any strategy applied needs to take into consideration that the vast majority of patients with acute heart failure, after initial treatment in the ED, are then treated in a general cardiology ward,” added Dr. Mueller.

This meant that intravenous nitrate infusion was not part of the GALACTIC trial; rather, sublingual and transdermal nitrates were used, explained Dr. Mueller. “Transdermal application has the beauty that if you have an adverse effect – and hypotension is the most dangerous one – you can immediately remove the patch, and thereby avoid any further harm.”

The two-part strategy tested in GALACTIC involved reducing cardiac filling pressures by maintaining or increasing organ perfusion, while also increasing “long-term lifesaving therapy” targeting the renin-angiotensin-aldosterone system during hospitalization, with a goal to continue optimal treatment long term.

ACE inhibitors or angiotensin receptor blockers were added on the second day of hospitalization for the intervention group, said Dr. Mueller, and “in the ideal setting, up-titrated very aggressively from day to day.

“However, as you know, up-titration to target dose is sometimes wishful thinking in this frail population,” he said, so the GALACTIC trial protocol included a scheme to back dosing off for hypotension, hypokalemia, or worsening renal function. Systolic BP guided how aggressively vasodilation and ACE inhibitor/angiotensin receptor blocker therapy were escalated.

In the end, 382 patients randomized to the intervention arm received early, intensive, and sustained vasodilation, and the 399 patients in the control arm received standard-of-care treatment according to ESC guidelines. These figures omit two patients in the standard-of-care arm who withdrew consent, but follow-up was otherwise complete, said Dr. Mueller. Physicians treating patients in both study arms had discretion to use such other therapies as loop diuretics, beta-blockers, aldosterone antagonists, and cardiac devices.

Adult patients coming to the ED with acute dyspnea classified as New York Heart Association class III or IV were eligible if they had brain natriuretic peptide (BNP) levels of at least 500 ng/L, or N-terminal of the prohormone BNP (NT-proBNP) levels of at least 2,000 ng/L.

Overall, patients enrolled in GALACTIC were in their late 70s, and women made up 37% of the population.

The actual median BNP for enrollees was about 1,250 ng/L, and the median NT-proBNP was just under 6,000 ng/L. The median left ventricular ejection fraction was 37%. About a third of patients had diabetes, and 85% had hypertension. Over half had known chronic heart failure, about a third had prior history of MI, and half of patients had atrial fibrillation at baseline.

“Signs of congestion were present in all patients, and over 90% had rales on physical examination,” said Dr. Mueller.

Patients who were destined for the ICU, those who had systolic BP below 100 mm Hg or marked creatinine elevation, or who required cardiopulmonary resuscitation were excluded. Also excluded were patients with known structural defects such as severe valvular stenosis, congenital heart disease, or hypertrophic obstructive cardiomyopathy. GALACTIC also excluded patients with isolated right ventricular failure caused by pulmonary hypertension.

Prespecified subgroup analyses compared women with men, and those younger than 75 years with older participants. Women saw a significantly higher hazard ratio for readmission or death, indicating a potential harm from the intervention, said Dr. Mueller. An additional analysis stratified patients by left ventricular ejection fraction. Aside from the intervention’s negative effect on women participating in the trial, no other subgroups benefited or were harmed by an early vasodilation strategy.

Alexandre Mebazaa, MD, the designated discussant for the presentation, said that, although the GALACTIC trial was neutral, it represents “an important step forward in acute heart failure.

“Congratulations: First, because we know that in the critically ill condition it’s very difficult to do trials,” and the GALACTIC investigators succeeded in enrolling patients within the first 5 hours of presentation to EDs, noted Dr. Mebazaa, professor of anesthesiology and critical care medicine at the Paris Diderot School of Medicine.

He added that GALACTIC succeeded in continuing vasodilator use beyond the 48-hour mark. “For the first time, you had the courage to go a little bit further down, and we see that patients got the drug with vasodilator properties for 2 days or more.”

However, the long recruitment period for GALACTIC – first enrollment began in 2007 – meant that the study design reflected a thought process about AHF that doesn’t necessarily reflect current practice, noted Dr. Mebazaa. “The trial was designed many years ago, and at that time, we were still thinking that giving very aggressive treatment in the first hours could have an impact.

“Now, when we will be treating patients with vasodilators with acute heart failure – at least myself and my group – I would really wonder whether there is still evidence in the world to support the use of those agents.”

Dr. Mueller noted limitations of the GALACTIC trial, including the lack of generalizability to patients with systolic hypotension or severe renal dysfunction, since these populations were excluded. Also, “the open-label design, which was mandated by the aim to test a strategy, not a single drug, may have introduced a bias in the unblinded assessment of dyspnea” during inpatient stay.

The study was funded by several Swiss research institutions and had no industry support. Dr. Mueller reported no relevant conflicts of interest. Dr. Mebazaa reported financial relationships with Roche, Service, Novartis, AstraZeneca, S-Form Pharma, 4Teen$4, Adrenomed, and Sphingotec.

[email protected]

SOURCE: Mueller C. ESC 2019, Hot Line Session 3.

The incidence and severity of hypertension was considerably higher in patients with B-cell malignancies treated with ibrutinib, according to a retrospective analysis.

Additionally, new or worsening hypertension was associated with a greater risk of major adverse cardiac events (MACE), including stroke, myocardial infarction, and cardiovascular-related death (hazard ratio, 2.17; 95% confidence interval, 1.08-4.38; P = .03).

“Despite ibrutinib’s benefits, cardiotoxicity has emerged as an increasingly important complication of this life-saving therapy,” Tyler Dickerson, PhD, of the Ohio State University, Columbus, and colleagues wrote in Blood.

The researchers retrospectively studied 562 consecutive patients with a lymphoid malignancy who received ibrutinib. Data was collected from patients treated at The Ohio State University’s Comprehensive Cancer Center during 2009-2016.

The mean age of study participants was 63.8 years, with a mean body mass index of 28.0 kg/m². Most of the patients included in the analysis were men.

The team assessed rates of new or worsening hypertension, as well as rates of other MACE. The observed rates were compared with Framingham Heart Study–predicted incident-hypertension rates. The effects of various antihypertensive drugs on ibrutinib-linked hypertension were also evaluated.

After a median follow-up of 30 months, 78.3% of patients who received ibrutinib had new or worsening hypertension using a systolic blood pressure cutoff of 130 mm Hg. Of these, 84.8% of cases had an “at least probable association with ibrutinib,” they reported.

Among the 215 patients with no baseline hypertension, 71.6% developed hypertension while on ibrutinib, with a mean increase in systolic blood pressure of 13.4 mm Hg. Among the 347 patients with baseline hypertension, 82.4% experienced a worsening of their hypertension.

“This relationship remained even after accounting for ibrutinib dose, and was not attenuated by the use of any specific anti-hypertensive class,” the researchers wrote.

The researchers observed MACE among 93 patients. This included 84 patients with new or worsening hypertension and 9 patients with stable or no hypertension. Most MACE events were of at least probable ibrutinib association, the researchers reported.

Overall, the cumulative incidence of new hypertension at 1 year was 442 per 1,000 person-years in the current study. This value is 12.9-fold higher than the Framingham Heart Study risk–predicted rate of 34 per 1,000 person-years.

“Given the expected continued increase in ibrutinib use, further studies characterizing the mechanisms, treatment, and implications of [hypertension] during ibrutinib use are needed,” the researchers wrote.

The study was funded by the National Institutes of Health, the D. Warren Brown Family Foundation, the Four Winds Foundation, and the Connie Brown CLL Research Fund. The authors reported financial affiliations with Janssen, Pharmacyclics, and other companies.

SOURCE: Dickerson T et al. Blood. 2019 Oct 3. doi: 10.1182/blood.2019000840.

The incidence and severity of hypertension was considerably higher in patients with B-cell malignancies treated with ibrutinib, according to a retrospective analysis.

Additionally, new or worsening hypertension was associated with a greater risk of major adverse cardiac events (MACE), including stroke, myocardial infarction, and cardiovascular-related death (hazard ratio, 2.17; 95% confidence interval, 1.08-4.38; P = .03).

“Despite ibrutinib’s benefits, cardiotoxicity has emerged as an increasingly important complication of this life-saving therapy,” Tyler Dickerson, PhD, of the Ohio State University, Columbus, and colleagues wrote in Blood.

The researchers retrospectively studied 562 consecutive patients with a lymphoid malignancy who received ibrutinib. Data was collected from patients treated at The Ohio State University’s Comprehensive Cancer Center during 2009-2016.

The mean age of study participants was 63.8 years, with a mean body mass index of 28.0 kg/m². Most of the patients included in the analysis were men.

The team assessed rates of new or worsening hypertension, as well as rates of other MACE. The observed rates were compared with Framingham Heart Study–predicted incident-hypertension rates. The effects of various antihypertensive drugs on ibrutinib-linked hypertension were also evaluated.

After a median follow-up of 30 months, 78.3% of patients who received ibrutinib had new or worsening hypertension using a systolic blood pressure cutoff of 130 mm Hg. Of these, 84.8% of cases had an “at least probable association with ibrutinib,” they reported.

Among the 215 patients with no baseline hypertension, 71.6% developed hypertension while on ibrutinib, with a mean increase in systolic blood pressure of 13.4 mm Hg. Among the 347 patients with baseline hypertension, 82.4% experienced a worsening of their hypertension.

“This relationship remained even after accounting for ibrutinib dose, and was not attenuated by the use of any specific anti-hypertensive class,” the researchers wrote.

The researchers observed MACE among 93 patients. This included 84 patients with new or worsening hypertension and 9 patients with stable or no hypertension. Most MACE events were of at least probable ibrutinib association, the researchers reported.

Overall, the cumulative incidence of new hypertension at 1 year was 442 per 1,000 person-years in the current study. This value is 12.9-fold higher than the Framingham Heart Study risk–predicted rate of 34 per 1,000 person-years.

“Given the expected continued increase in ibrutinib use, further studies characterizing the mechanisms, treatment, and implications of [hypertension] during ibrutinib use are needed,” the researchers wrote.

The study was funded by the National Institutes of Health, the D. Warren Brown Family Foundation, the Four Winds Foundation, and the Connie Brown CLL Research Fund. The authors reported financial affiliations with Janssen, Pharmacyclics, and other companies.

SOURCE: Dickerson T et al. Blood. 2019 Oct 3. doi: 10.1182/blood.2019000840.

The incidence and severity of hypertension was considerably higher in patients with B-cell malignancies treated with ibrutinib, according to a retrospective analysis.

Additionally, new or worsening hypertension was associated with a greater risk of major adverse cardiac events (MACE), including stroke, myocardial infarction, and cardiovascular-related death (hazard ratio, 2.17; 95% confidence interval, 1.08-4.38; P = .03).

“Despite ibrutinib’s benefits, cardiotoxicity has emerged as an increasingly important complication of this life-saving therapy,” Tyler Dickerson, PhD, of the Ohio State University, Columbus, and colleagues wrote in Blood.

The researchers retrospectively studied 562 consecutive patients with a lymphoid malignancy who received ibrutinib. Data was collected from patients treated at The Ohio State University’s Comprehensive Cancer Center during 2009-2016.

The mean age of study participants was 63.8 years, with a mean body mass index of 28.0 kg/m². Most of the patients included in the analysis were men.

The team assessed rates of new or worsening hypertension, as well as rates of other MACE. The observed rates were compared with Framingham Heart Study–predicted incident-hypertension rates. The effects of various antihypertensive drugs on ibrutinib-linked hypertension were also evaluated.

After a median follow-up of 30 months, 78.3% of patients who received ibrutinib had new or worsening hypertension using a systolic blood pressure cutoff of 130 mm Hg. Of these, 84.8% of cases had an “at least probable association with ibrutinib,” they reported.

Among the 215 patients with no baseline hypertension, 71.6% developed hypertension while on ibrutinib, with a mean increase in systolic blood pressure of 13.4 mm Hg. Among the 347 patients with baseline hypertension, 82.4% experienced a worsening of their hypertension.

“This relationship remained even after accounting for ibrutinib dose, and was not attenuated by the use of any specific anti-hypertensive class,” the researchers wrote.

The researchers observed MACE among 93 patients. This included 84 patients with new or worsening hypertension and 9 patients with stable or no hypertension. Most MACE events were of at least probable ibrutinib association, the researchers reported.

Overall, the cumulative incidence of new hypertension at 1 year was 442 per 1,000 person-years in the current study. This value is 12.9-fold higher than the Framingham Heart Study risk–predicted rate of 34 per 1,000 person-years.

“Given the expected continued increase in ibrutinib use, further studies characterizing the mechanisms, treatment, and implications of [hypertension] during ibrutinib use are needed,” the researchers wrote.

The study was funded by the National Institutes of Health, the D. Warren Brown Family Foundation, the Four Winds Foundation, and the Connie Brown CLL Research Fund. The authors reported financial affiliations with Janssen, Pharmacyclics, and other companies.

SOURCE: Dickerson T et al. Blood. 2019 Oct 3. doi: 10.1182/blood.2019000840.

A pooled analysis suggests adverse cytogenetics are a key factor negatively impacting outcomes in patients with NPM1^mut/FLT3-ITD^neg/low acute myeloid leukemia (AML).

National Institutes of Health/Wikimedia Commons/Public Domain

In patients with adverse chromosomal abnormalities, NPM1 mutational status was found not to confer a favorable outcome. The findings suggest cytogenetic risk outweighs molecular risk in patients with NPM1 mutations and the FLT3-ITD^neg/low genotype.

“Patients carrying adverse-risk cytogenetics shared a virtually identical unfavorable outcome, regardless of whether the otherwise beneficial NPM1^mut/FLT3-ITD^neg/low status was present. The type of the adverse chromosomal abnormality did not seem to influence this effect, although low numbers might obscure detection of heterogeneity among individual aberrations,” Linus Angenendt, MD, of University Hospital Munster (Germany) and colleagues, wrote in the Journal of Clinical Oncology.

The researchers retrospectively analyzed 2,426 patients with NPM1^mut/FLT3-ITD^neg/low AML. Of these, 17.6% had an abnormal karyotype, and 3.4% had adverse-risk chromosomal aberrations.

Prior to analysis, individual patient data were pooled from nine international AML study group registries or treatment centers.

After analysis, the researchers found that adverse cytogenetics were associated with inferior complete remission rates (66.3%), compared with in patients with normal karyotype or intermediate-risk cytogenetic abnormalities (87.7% and 86.0%, respectively; P less than .001). The complete remission rates for the NPM1^mut/FLT3-ITD^neg/low AML adverse cytogenetics group was similar to patients with NPM1^wt/FLT3-ITD^neg/low and adverse cytogenetic abnormalities (66.3% vs. 57.5%).

Five-year event-free survival rates and overall survival rates were also lower in patients with NPM1^mut/FLT3-ITD^neg/low AML and adverse cytogenetics, compared with patients with normal karyotype or intermediate-risk cytogenetic abnormalities (P less than .001).

“Even though the combination of an NPM1 mutation with these abnormalities is rare, the prognostic effect of adverse cytogenetics in NPM1^mut AML has important implications for postremission treatment decisions, in particular, the current recommendation that patients who are NPM1^mut/FLT3-ITD^neg/low not receive allogeneic hematopoietic stem cell transplantation (HSCT), given their presumed low risk of relapse might be altered if the adverse karyotype increased the risk,” they wrote.

The type of chromosomal aberration did not appear to impact this effect, but the small sample size may have hindered the ability to detect a difference between different abnormalities, the researchers noted.

One key limitation of the study was the retrospective design. As a result, in patients with an abnormal karyotype, some genetic analyses could have been underutilized.

“These results demand additional validation within prospective trials,” the researchers concluded.

The study was funded by the University of Munster Medical School, the German Research Foundation, the French government, the Ministry of Health of the Czech Republic, and others. The authors reported financial affiliations with numerous pharmaceutical companies.

SOURCE: Angenendt L et al. J Clin Oncol. 2019 Oct 10;37(29):2632-42.

A pooled analysis suggests adverse cytogenetics are a key factor negatively impacting outcomes in patients with NPM1^mut/FLT3-ITD^neg/low acute myeloid leukemia (AML).

National Institutes of Health/Wikimedia Commons/Public Domain

In patients with adverse chromosomal abnormalities, NPM1 mutational status was found not to confer a favorable outcome. The findings suggest cytogenetic risk outweighs molecular risk in patients with NPM1 mutations and the FLT3-ITD^neg/low genotype.

“Patients carrying adverse-risk cytogenetics shared a virtually identical unfavorable outcome, regardless of whether the otherwise beneficial NPM1^mut/FLT3-ITD^neg/low status was present. The type of the adverse chromosomal abnormality did not seem to influence this effect, although low numbers might obscure detection of heterogeneity among individual aberrations,” Linus Angenendt, MD, of University Hospital Munster (Germany) and colleagues, wrote in the Journal of Clinical Oncology.

The researchers retrospectively analyzed 2,426 patients with NPM1^mut/FLT3-ITD^neg/low AML. Of these, 17.6% had an abnormal karyotype, and 3.4% had adverse-risk chromosomal aberrations.

Prior to analysis, individual patient data were pooled from nine international AML study group registries or treatment centers.

After analysis, the researchers found that adverse cytogenetics were associated with inferior complete remission rates (66.3%), compared with in patients with normal karyotype or intermediate-risk cytogenetic abnormalities (87.7% and 86.0%, respectively; P less than .001). The complete remission rates for the NPM1^mut/FLT3-ITD^neg/low AML adverse cytogenetics group was similar to patients with NPM1^wt/FLT3-ITD^neg/low and adverse cytogenetic abnormalities (66.3% vs. 57.5%).

Five-year event-free survival rates and overall survival rates were also lower in patients with NPM1^mut/FLT3-ITD^neg/low AML and adverse cytogenetics, compared with patients with normal karyotype or intermediate-risk cytogenetic abnormalities (P less than .001).

“Even though the combination of an NPM1 mutation with these abnormalities is rare, the prognostic effect of adverse cytogenetics in NPM1^mut AML has important implications for postremission treatment decisions, in particular, the current recommendation that patients who are NPM1^mut/FLT3-ITD^neg/low not receive allogeneic hematopoietic stem cell transplantation (HSCT), given their presumed low risk of relapse might be altered if the adverse karyotype increased the risk,” they wrote.

The type of chromosomal aberration did not appear to impact this effect, but the small sample size may have hindered the ability to detect a difference between different abnormalities, the researchers noted.

One key limitation of the study was the retrospective design. As a result, in patients with an abnormal karyotype, some genetic analyses could have been underutilized.

“These results demand additional validation within prospective trials,” the researchers concluded.

The study was funded by the University of Munster Medical School, the German Research Foundation, the French government, the Ministry of Health of the Czech Republic, and others. The authors reported financial affiliations with numerous pharmaceutical companies.

SOURCE: Angenendt L et al. J Clin Oncol. 2019 Oct 10;37(29):2632-42.

A pooled analysis suggests adverse cytogenetics are a key factor negatively impacting outcomes in patients with NPM1^mut/FLT3-ITD^neg/low acute myeloid leukemia (AML).

National Institutes of Health/Wikimedia Commons/Public Domain

In patients with adverse chromosomal abnormalities, NPM1 mutational status was found not to confer a favorable outcome. The findings suggest cytogenetic risk outweighs molecular risk in patients with NPM1 mutations and the FLT3-ITD^neg/low genotype.

“Patients carrying adverse-risk cytogenetics shared a virtually identical unfavorable outcome, regardless of whether the otherwise beneficial NPM1^mut/FLT3-ITD^neg/low status was present. The type of the adverse chromosomal abnormality did not seem to influence this effect, although low numbers might obscure detection of heterogeneity among individual aberrations,” Linus Angenendt, MD, of University Hospital Munster (Germany) and colleagues, wrote in the Journal of Clinical Oncology.

The researchers retrospectively analyzed 2,426 patients with NPM1^mut/FLT3-ITD^neg/low AML. Of these, 17.6% had an abnormal karyotype, and 3.4% had adverse-risk chromosomal aberrations.

Prior to analysis, individual patient data were pooled from nine international AML study group registries or treatment centers.

After analysis, the researchers found that adverse cytogenetics were associated with inferior complete remission rates (66.3%), compared with in patients with normal karyotype or intermediate-risk cytogenetic abnormalities (87.7% and 86.0%, respectively; P less than .001). The complete remission rates for the NPM1^mut/FLT3-ITD^neg/low AML adverse cytogenetics group was similar to patients with NPM1^wt/FLT3-ITD^neg/low and adverse cytogenetic abnormalities (66.3% vs. 57.5%).

Five-year event-free survival rates and overall survival rates were also lower in patients with NPM1^mut/FLT3-ITD^neg/low AML and adverse cytogenetics, compared with patients with normal karyotype or intermediate-risk cytogenetic abnormalities (P less than .001).

“Even though the combination of an NPM1 mutation with these abnormalities is rare, the prognostic effect of adverse cytogenetics in NPM1^mut AML has important implications for postremission treatment decisions, in particular, the current recommendation that patients who are NPM1^mut/FLT3-ITD^neg/low not receive allogeneic hematopoietic stem cell transplantation (HSCT), given their presumed low risk of relapse might be altered if the adverse karyotype increased the risk,” they wrote.

The type of chromosomal aberration did not appear to impact this effect, but the small sample size may have hindered the ability to detect a difference between different abnormalities, the researchers noted.

One key limitation of the study was the retrospective design. As a result, in patients with an abnormal karyotype, some genetic analyses could have been underutilized.

“These results demand additional validation within prospective trials,” the researchers concluded.

The study was funded by the University of Munster Medical School, the German Research Foundation, the French government, the Ministry of Health of the Czech Republic, and others. The authors reported financial affiliations with numerous pharmaceutical companies.

SOURCE: Angenendt L et al. J Clin Oncol. 2019 Oct 10;37(29):2632-42.

For more information about upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.

UPCOMING EVENTS

Dec. 9-10, 11-12, 18-19, 2019; Jan. 15-16, 22-23; Feb. 12-13, Mar. 10-11, 11-12, 25-26; Apr. 15-16; May 13-14, 2020
Two-Day, In-Depth Coding Seminar by McVey Associates, Inc.
Become a certified GI coder with a 2-day, in-depth training course provided by McVey Associates, Inc.
Anaheim, Calif. (12/9-10); Houston, Tex. (12/11-12); New Orleans, La. (12/18-19); Phoenix, Ariz. (12/18-19); Pittsburgh, Pa. (1/15-16); Dallas, Tex. (1/22-23); Hartford, Conn. (2/12-13); Orlando, Fla. (3/10-11); Novi, Mich. (3/11-12); Charlotte, N.C. (3/25-26); Columbus, Ohio (4/15-16); Chicago, Ill. (5/13-14)

Jan. 23–25, 2020
2020 Crohn’s & Colitis Congress®
Gain a multidisciplinary perspective on treating inflammatory bowel diseases (IBD). Join health care professionals and researchers at the Crohn’s & Colitis Congress^® for the premier conference on IBD. Discover different perspectives, leave with practical information you can immediately implement, and hear about potential treatments on the horizon.
Austin, Tex.

Jan. 23–25, 2020
Gastrointestinal Cancers Symposium
Designed for clinicians, scientists, and all other members of the cancer care and research community, the 2020 Gastrointestinal Cancers Symposium will feature a wide array of multidisciplinary topics and expert faculty will offer insights on the application of gastrointestinal advances in: cancers of the esophagus and stomach, pancreas, small bowel and hepatobiliary tract, and the colon, rectum, and anus.
San Francisco, Calif.

Feb. 8-9, 2020
2020 Academic Skills Workshop
A free biannual meeting for fellows and early-career GIs that is implemented in conjunction with the AASLD. Topics range from leveraging mentor-mentee relationships, promotion strategies, and insights on writing grants. The application deadline is Nov. 18, 2019.
Charlotte, N.C.
 

Feb. 20; Mar. 24, 2020
Coding and Reimbursement Solutions by McVey Associates, Inc.
Improve the efficiency and performance of your practice by staying current on the latest reimbursement, coding and compliance changes.
Knoxville, Tenn. (2/20); Birmingham, Ala. (3/24)
 

May 2-5, 2020
Digestive Disease Week® (DDW)
Digestive Disease Week^® (DDW) is the world’s leading educational forum for academicians, clinicians, researchers, students, and trainees working in gastroenterology, hepatology, GI endoscopy, gastrointestinal surgery, and related fields. Whether you work in patient care, research, education, or administration, the DDW program offers something for you. Abstract submissions will be due on Dec. 1, and registration will open in January 2020.
Chicago, Ill.
 

June 3-6, 2020
2020 AGA Tech Summit
Visit https://techsummit.gastro.org/ for more details.
San Francisco, Calif.
 

AWARDS DEADLINES

AGA Fellow Abstract Award
This $500 travel award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW). The top-scoring abstract will be designated the Fellow Abstract of the Year and receive a $1,000 award.
Application Deadline: Feb. 26, 2020

AGA Student Abstract Award
This $500 travel award supports recipients who are graduate students, medical students, or medical residents (residents up to postgraduate year three) giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW).
Application Deadline: Feb. 26, 2020

AGA-Moti L. & Kamla Rustgi International Travel Awards
This $750 travel award supports recipients who are young (i.e., 35 years of age or younger at the time of DDW) basic, translational or clinical investigators residing outside North America to support travel and related expenses to attend Digestive Disease Week^® (DDW).
Application Deadline: Feb. 26, 2020
 

For more information about upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.

UPCOMING EVENTS

Dec. 9-10, 11-12, 18-19, 2019; Jan. 15-16, 22-23; Feb. 12-13, Mar. 10-11, 11-12, 25-26; Apr. 15-16; May 13-14, 2020
Two-Day, In-Depth Coding Seminar by McVey Associates, Inc.
Become a certified GI coder with a 2-day, in-depth training course provided by McVey Associates, Inc.
Anaheim, Calif. (12/9-10); Houston, Tex. (12/11-12); New Orleans, La. (12/18-19); Phoenix, Ariz. (12/18-19); Pittsburgh, Pa. (1/15-16); Dallas, Tex. (1/22-23); Hartford, Conn. (2/12-13); Orlando, Fla. (3/10-11); Novi, Mich. (3/11-12); Charlotte, N.C. (3/25-26); Columbus, Ohio (4/15-16); Chicago, Ill. (5/13-14)

Jan. 23–25, 2020
2020 Crohn’s & Colitis Congress®
Gain a multidisciplinary perspective on treating inflammatory bowel diseases (IBD). Join health care professionals and researchers at the Crohn’s & Colitis Congress^® for the premier conference on IBD. Discover different perspectives, leave with practical information you can immediately implement, and hear about potential treatments on the horizon.
Austin, Tex.

Jan. 23–25, 2020
Gastrointestinal Cancers Symposium
Designed for clinicians, scientists, and all other members of the cancer care and research community, the 2020 Gastrointestinal Cancers Symposium will feature a wide array of multidisciplinary topics and expert faculty will offer insights on the application of gastrointestinal advances in: cancers of the esophagus and stomach, pancreas, small bowel and hepatobiliary tract, and the colon, rectum, and anus.
San Francisco, Calif.

Feb. 8-9, 2020
2020 Academic Skills Workshop
A free biannual meeting for fellows and early-career GIs that is implemented in conjunction with the AASLD. Topics range from leveraging mentor-mentee relationships, promotion strategies, and insights on writing grants. The application deadline is Nov. 18, 2019.
Charlotte, N.C.
 

Feb. 20; Mar. 24, 2020
Coding and Reimbursement Solutions by McVey Associates, Inc.
Improve the efficiency and performance of your practice by staying current on the latest reimbursement, coding and compliance changes.
Knoxville, Tenn. (2/20); Birmingham, Ala. (3/24)
 

May 2-5, 2020
Digestive Disease Week® (DDW)
Digestive Disease Week^® (DDW) is the world’s leading educational forum for academicians, clinicians, researchers, students, and trainees working in gastroenterology, hepatology, GI endoscopy, gastrointestinal surgery, and related fields. Whether you work in patient care, research, education, or administration, the DDW program offers something for you. Abstract submissions will be due on Dec. 1, and registration will open in January 2020.
Chicago, Ill.
 

June 3-6, 2020
2020 AGA Tech Summit
Visit https://techsummit.gastro.org/ for more details.
San Francisco, Calif.
 

AWARDS DEADLINES

AGA Fellow Abstract Award
This $500 travel award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW). The top-scoring abstract will be designated the Fellow Abstract of the Year and receive a $1,000 award.
Application Deadline: Feb. 26, 2020

AGA Student Abstract Award
This $500 travel award supports recipients who are graduate students, medical students, or medical residents (residents up to postgraduate year three) giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW).
Application Deadline: Feb. 26, 2020

AGA-Moti L. & Kamla Rustgi International Travel Awards
This $750 travel award supports recipients who are young (i.e., 35 years of age or younger at the time of DDW) basic, translational or clinical investigators residing outside North America to support travel and related expenses to attend Digestive Disease Week^® (DDW).
Application Deadline: Feb. 26, 2020
 

For more information about upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.

UPCOMING EVENTS

Dec. 9-10, 11-12, 18-19, 2019; Jan. 15-16, 22-23; Feb. 12-13, Mar. 10-11, 11-12, 25-26; Apr. 15-16; May 13-14, 2020
Two-Day, In-Depth Coding Seminar by McVey Associates, Inc.
Become a certified GI coder with a 2-day, in-depth training course provided by McVey Associates, Inc.
Anaheim, Calif. (12/9-10); Houston, Tex. (12/11-12); New Orleans, La. (12/18-19); Phoenix, Ariz. (12/18-19); Pittsburgh, Pa. (1/15-16); Dallas, Tex. (1/22-23); Hartford, Conn. (2/12-13); Orlando, Fla. (3/10-11); Novi, Mich. (3/11-12); Charlotte, N.C. (3/25-26); Columbus, Ohio (4/15-16); Chicago, Ill. (5/13-14)

Jan. 23–25, 2020
2020 Crohn’s & Colitis Congress®
Gain a multidisciplinary perspective on treating inflammatory bowel diseases (IBD). Join health care professionals and researchers at the Crohn’s & Colitis Congress^® for the premier conference on IBD. Discover different perspectives, leave with practical information you can immediately implement, and hear about potential treatments on the horizon.
Austin, Tex.

Jan. 23–25, 2020
Gastrointestinal Cancers Symposium
Designed for clinicians, scientists, and all other members of the cancer care and research community, the 2020 Gastrointestinal Cancers Symposium will feature a wide array of multidisciplinary topics and expert faculty will offer insights on the application of gastrointestinal advances in: cancers of the esophagus and stomach, pancreas, small bowel and hepatobiliary tract, and the colon, rectum, and anus.
San Francisco, Calif.

Feb. 8-9, 2020
2020 Academic Skills Workshop
A free biannual meeting for fellows and early-career GIs that is implemented in conjunction with the AASLD. Topics range from leveraging mentor-mentee relationships, promotion strategies, and insights on writing grants. The application deadline is Nov. 18, 2019.
Charlotte, N.C.
 

Feb. 20; Mar. 24, 2020
Coding and Reimbursement Solutions by McVey Associates, Inc.
Improve the efficiency and performance of your practice by staying current on the latest reimbursement, coding and compliance changes.
Knoxville, Tenn. (2/20); Birmingham, Ala. (3/24)
 

May 2-5, 2020
Digestive Disease Week® (DDW)
Digestive Disease Week^® (DDW) is the world’s leading educational forum for academicians, clinicians, researchers, students, and trainees working in gastroenterology, hepatology, GI endoscopy, gastrointestinal surgery, and related fields. Whether you work in patient care, research, education, or administration, the DDW program offers something for you. Abstract submissions will be due on Dec. 1, and registration will open in January 2020.
Chicago, Ill.
 

June 3-6, 2020
2020 AGA Tech Summit
Visit https://techsummit.gastro.org/ for more details.
San Francisco, Calif.
 

AWARDS DEADLINES

AGA Fellow Abstract Award
This $500 travel award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW). The top-scoring abstract will be designated the Fellow Abstract of the Year and receive a $1,000 award.
Application Deadline: Feb. 26, 2020

AGA Student Abstract Award
This $500 travel award supports recipients who are graduate students, medical students, or medical residents (residents up to postgraduate year three) giving abstract-based oral or poster presentations at Digestive Disease Week^® (DDW).
Application Deadline: Feb. 26, 2020

AGA-Moti L. & Kamla Rustgi International Travel Awards
This $750 travel award supports recipients who are young (i.e., 35 years of age or younger at the time of DDW) basic, translational or clinical investigators residing outside North America to support travel and related expenses to attend Digestive Disease Week^® (DDW).
Application Deadline: Feb. 26, 2020
 

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.