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Do hospitalists improve inpatient outcomes?
Long continues the debate on what impact hospitalists have on inpatient outcomes. This issue has been playing out in the medical literature for 20 years, since the coining of the term in 1997. In a recent iteration of the debate, a study was published in JAMA Internal Medicine entitled “Comparison of Hospital Resource Use and Outcomes Among Hospitalists, Primary Care Physicians, and Other Generalists.”
The study retrospectively evaluated health care resources and outcomes from over a half-million Medicare beneficiaries hospitalized in 2013 for 20 common diagnosis-related groups, by type of physician provider (hospitalist, their primary care physician, or other generalist). The study found that nonhospitalists used more consultations and had longer lengths of stays, compared with hospitalists. In addition, relative to hospitalists, PCPs were more likely to discharge patients to home, had similar readmission rates, and lower 30-day mortality rates, but generalists were less likely to discharge patients home, had higher readmission rates, and higher mortality rates.
As hospitalists, we need to understand and acknowledge that most of our patients are “brand new” to us, and it is paramount that we use all available resources to gain a deep understanding of the patient in as short a time as possible. For example, ensuring all medical records available are reviewed, at least as much as possible, including a medical list (including a medication reconciliation). Interviewing family members or caregivers is also obviously a “best practice.” As well, having the insight of the PCP in these patients’ care is unquestionably good for us, for the PCP, and for the patient.
With good communication processes and an eye for excellence in care transitions, hospitalists can and should achieve the best outcomes for all of their patients. I look forward to more research in this arena, including a better understanding of the mechanisms by which we can all reliably produce excellent outcomes for the patients we serve.
Read the full post at hospitalleader.org.
Also on The Hospital Leader …
• Locums vs. F/T Hospitalists: Do Temps Stack Up? by Brad Flansbaum, DO, MPH, MHM
• Rounds: Are We Spinning Our Wheels? by Vineet Arora, MD, MPP, MHM
• Up Your Game in APP Integration by Tracy Cardin, ACNP-BC, SFHM
Long continues the debate on what impact hospitalists have on inpatient outcomes. This issue has been playing out in the medical literature for 20 years, since the coining of the term in 1997. In a recent iteration of the debate, a study was published in JAMA Internal Medicine entitled “Comparison of Hospital Resource Use and Outcomes Among Hospitalists, Primary Care Physicians, and Other Generalists.”
The study retrospectively evaluated health care resources and outcomes from over a half-million Medicare beneficiaries hospitalized in 2013 for 20 common diagnosis-related groups, by type of physician provider (hospitalist, their primary care physician, or other generalist). The study found that nonhospitalists used more consultations and had longer lengths of stays, compared with hospitalists. In addition, relative to hospitalists, PCPs were more likely to discharge patients to home, had similar readmission rates, and lower 30-day mortality rates, but generalists were less likely to discharge patients home, had higher readmission rates, and higher mortality rates.
As hospitalists, we need to understand and acknowledge that most of our patients are “brand new” to us, and it is paramount that we use all available resources to gain a deep understanding of the patient in as short a time as possible. For example, ensuring all medical records available are reviewed, at least as much as possible, including a medical list (including a medication reconciliation). Interviewing family members or caregivers is also obviously a “best practice.” As well, having the insight of the PCP in these patients’ care is unquestionably good for us, for the PCP, and for the patient.
With good communication processes and an eye for excellence in care transitions, hospitalists can and should achieve the best outcomes for all of their patients. I look forward to more research in this arena, including a better understanding of the mechanisms by which we can all reliably produce excellent outcomes for the patients we serve.
Read the full post at hospitalleader.org.
Also on The Hospital Leader …
• Locums vs. F/T Hospitalists: Do Temps Stack Up? by Brad Flansbaum, DO, MPH, MHM
• Rounds: Are We Spinning Our Wheels? by Vineet Arora, MD, MPP, MHM
• Up Your Game in APP Integration by Tracy Cardin, ACNP-BC, SFHM
Long continues the debate on what impact hospitalists have on inpatient outcomes. This issue has been playing out in the medical literature for 20 years, since the coining of the term in 1997. In a recent iteration of the debate, a study was published in JAMA Internal Medicine entitled “Comparison of Hospital Resource Use and Outcomes Among Hospitalists, Primary Care Physicians, and Other Generalists.”
The study retrospectively evaluated health care resources and outcomes from over a half-million Medicare beneficiaries hospitalized in 2013 for 20 common diagnosis-related groups, by type of physician provider (hospitalist, their primary care physician, or other generalist). The study found that nonhospitalists used more consultations and had longer lengths of stays, compared with hospitalists. In addition, relative to hospitalists, PCPs were more likely to discharge patients to home, had similar readmission rates, and lower 30-day mortality rates, but generalists were less likely to discharge patients home, had higher readmission rates, and higher mortality rates.
As hospitalists, we need to understand and acknowledge that most of our patients are “brand new” to us, and it is paramount that we use all available resources to gain a deep understanding of the patient in as short a time as possible. For example, ensuring all medical records available are reviewed, at least as much as possible, including a medical list (including a medication reconciliation). Interviewing family members or caregivers is also obviously a “best practice.” As well, having the insight of the PCP in these patients’ care is unquestionably good for us, for the PCP, and for the patient.
With good communication processes and an eye for excellence in care transitions, hospitalists can and should achieve the best outcomes for all of their patients. I look forward to more research in this arena, including a better understanding of the mechanisms by which we can all reliably produce excellent outcomes for the patients we serve.
Read the full post at hospitalleader.org.
Also on The Hospital Leader …
• Locums vs. F/T Hospitalists: Do Temps Stack Up? by Brad Flansbaum, DO, MPH, MHM
• Rounds: Are We Spinning Our Wheels? by Vineet Arora, MD, MPP, MHM
• Up Your Game in APP Integration by Tracy Cardin, ACNP-BC, SFHM
Skin rollers
, but only a few actually have any scientific data or clinical studies supporting their claims. In general, these rollers promise to increase collagen, depuff the skin, lift and firm, increase circulation, increase oxygenation, and decrease inflammation. But no clinically significant results have been reported with most of these over-the-counter devices. Furthermore, not every roller is meant for every skin type – and some should stay within the hands of an experienced professional.
Ice rollers have been used for many years and are very effective to cool the skin for in-office procedures. They are drum-shaped stainless steel rollers that are left in the freezer and cool the epidermis upon application. At-home ice rollers cause immediate vasoconstriction and are a quick fix for periorbital edema or skin erythema. Three-dimensional roller face massagers are simply a massage tool and can be used on any skin type to increase facial circulation; they do not provide any visible clinical benefits. Nanocurrent or vibrating rollers use nanocurrents and vibration alongside a conductor gel to glide across the skin; they massage the skin and help topically applied agents penetrate into the stratum corneum.
Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
References
Orentreich DS et al. Dermatol Surg. 1995;21(6):543-9.
Aust MC et al. Plast Reconstr Surg. 2008;21(4):1421-9.Fernandes D et al. Clin Dermatol. 2008 Mar-Apr;26(2):192-9.
Nair PA et al. GMJ. 2014;69:24-7.
, but only a few actually have any scientific data or clinical studies supporting their claims. In general, these rollers promise to increase collagen, depuff the skin, lift and firm, increase circulation, increase oxygenation, and decrease inflammation. But no clinically significant results have been reported with most of these over-the-counter devices. Furthermore, not every roller is meant for every skin type – and some should stay within the hands of an experienced professional.
Ice rollers have been used for many years and are very effective to cool the skin for in-office procedures. They are drum-shaped stainless steel rollers that are left in the freezer and cool the epidermis upon application. At-home ice rollers cause immediate vasoconstriction and are a quick fix for periorbital edema or skin erythema. Three-dimensional roller face massagers are simply a massage tool and can be used on any skin type to increase facial circulation; they do not provide any visible clinical benefits. Nanocurrent or vibrating rollers use nanocurrents and vibration alongside a conductor gel to glide across the skin; they massage the skin and help topically applied agents penetrate into the stratum corneum.
Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
References
Orentreich DS et al. Dermatol Surg. 1995;21(6):543-9.
Aust MC et al. Plast Reconstr Surg. 2008;21(4):1421-9.Fernandes D et al. Clin Dermatol. 2008 Mar-Apr;26(2):192-9.
Nair PA et al. GMJ. 2014;69:24-7.
, but only a few actually have any scientific data or clinical studies supporting their claims. In general, these rollers promise to increase collagen, depuff the skin, lift and firm, increase circulation, increase oxygenation, and decrease inflammation. But no clinically significant results have been reported with most of these over-the-counter devices. Furthermore, not every roller is meant for every skin type – and some should stay within the hands of an experienced professional.
Ice rollers have been used for many years and are very effective to cool the skin for in-office procedures. They are drum-shaped stainless steel rollers that are left in the freezer and cool the epidermis upon application. At-home ice rollers cause immediate vasoconstriction and are a quick fix for periorbital edema or skin erythema. Three-dimensional roller face massagers are simply a massage tool and can be used on any skin type to increase facial circulation; they do not provide any visible clinical benefits. Nanocurrent or vibrating rollers use nanocurrents and vibration alongside a conductor gel to glide across the skin; they massage the skin and help topically applied agents penetrate into the stratum corneum.
Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
References
Orentreich DS et al. Dermatol Surg. 1995;21(6):543-9.
Aust MC et al. Plast Reconstr Surg. 2008;21(4):1421-9.Fernandes D et al. Clin Dermatol. 2008 Mar-Apr;26(2):192-9.
Nair PA et al. GMJ. 2014;69:24-7.
‘Fast food swamps’ linked to type 1 diabetes
Areas with a high density of fast food outlets are associated with a greater prevalence of type 1 diabetes but not type 2 diabetes, according to new research.
These findings come from an analysis of emergency claims data for 5 million adults and 1.6 million children in New York who visited an emergency department at least once during 2009-2013. Researchers also looked at sociodemographic data for the area from community surveys and used local authorities’ inspection data to characterize local restaurant and retail food environments.
But when the analysis was adjusted to account for a range of factors, including age, sex, ethnicity, household income, and employment rates, the association between fast food swamps and diabetes was significant for pediatric type 1 diabetes only.
“Given the rising prevalence of type 1 diabetes, there has been increasing belief that certain environmental influences are contributing sharply to these increases,” wrote David C. Lee, MD, New York University Langone Health, and his coauthors. “There is some emerging literature which suggests that pregnant women in adverse food environments may have a higher likelihood of gestational diabetes, which some believe may affect health outcomes in their offspring.”
The study also failed to find an influence of retail food swamps – areas with more bodegas or small convenience stores within a 1-mile radius – on the prevalence of either type 1 or type 2 diabetes, in either adults or children. When researchers extended this to a 2-mile radius, they did find a significantly higher prevalence of pediatric type 1 diabetes associated with retail food swamps but a significantly lower prevalence of adult type 1 diabetes.
“This result may suggest that the retail food environment does not have a strong association with local diabetes prevalence or may be due to how we measured the retail food environment,” they wrote.
In general, the study found that the prevalence of adult and pediatric type 1 diabetes was significantly lower in most black neighborhoods, while the prevalence of adult type 1 diabetes was significantly lower in most Hispanic neighborhoods. Higher-income neighborhoods showed a significantly higher prevalence of pediatric type 1 diabetes.
The prevalence of type 2 diabetes in adults was significantly higher in low-income neighborhoods and those with more elderly residents, while the highest rates of pediatric type 2 diabetes were found in black neighborhoods.
The authors commented that they were surprised that their data did not show a higher prevalence of adult type 2 diabetes in black neighborhoods.
“In our multivariate analysis, older age and lower income were the only demographic or socioeconomic factors associated with higher adult type 2 diabetes prevalence,” they wrote.
Their use of ED surveillance data may have skewed the findings toward individuals more likely to visit those departments, namely Medicaid patients. But they suggested this would be balanced by the fact that the analysis was based on small geographic areas.
“Overall, our results may suggest that the physical food environment may not play as strong a role in characterizing the risk of type 2 diabetes among children and that other factors such as genetics, health behaviors, environmental exposures, or family influences may play more important roles.”
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation. No conflicts of interest were declared.
SOURCE: Lee DC et al. J Endocr Soc. 2018. Apr 17. doi: 10.1210/js.2018-00001.
Areas with a high density of fast food outlets are associated with a greater prevalence of type 1 diabetes but not type 2 diabetes, according to new research.
These findings come from an analysis of emergency claims data for 5 million adults and 1.6 million children in New York who visited an emergency department at least once during 2009-2013. Researchers also looked at sociodemographic data for the area from community surveys and used local authorities’ inspection data to characterize local restaurant and retail food environments.
But when the analysis was adjusted to account for a range of factors, including age, sex, ethnicity, household income, and employment rates, the association between fast food swamps and diabetes was significant for pediatric type 1 diabetes only.
“Given the rising prevalence of type 1 diabetes, there has been increasing belief that certain environmental influences are contributing sharply to these increases,” wrote David C. Lee, MD, New York University Langone Health, and his coauthors. “There is some emerging literature which suggests that pregnant women in adverse food environments may have a higher likelihood of gestational diabetes, which some believe may affect health outcomes in their offspring.”
The study also failed to find an influence of retail food swamps – areas with more bodegas or small convenience stores within a 1-mile radius – on the prevalence of either type 1 or type 2 diabetes, in either adults or children. When researchers extended this to a 2-mile radius, they did find a significantly higher prevalence of pediatric type 1 diabetes associated with retail food swamps but a significantly lower prevalence of adult type 1 diabetes.
“This result may suggest that the retail food environment does not have a strong association with local diabetes prevalence or may be due to how we measured the retail food environment,” they wrote.
In general, the study found that the prevalence of adult and pediatric type 1 diabetes was significantly lower in most black neighborhoods, while the prevalence of adult type 1 diabetes was significantly lower in most Hispanic neighborhoods. Higher-income neighborhoods showed a significantly higher prevalence of pediatric type 1 diabetes.
The prevalence of type 2 diabetes in adults was significantly higher in low-income neighborhoods and those with more elderly residents, while the highest rates of pediatric type 2 diabetes were found in black neighborhoods.
The authors commented that they were surprised that their data did not show a higher prevalence of adult type 2 diabetes in black neighborhoods.
“In our multivariate analysis, older age and lower income were the only demographic or socioeconomic factors associated with higher adult type 2 diabetes prevalence,” they wrote.
Their use of ED surveillance data may have skewed the findings toward individuals more likely to visit those departments, namely Medicaid patients. But they suggested this would be balanced by the fact that the analysis was based on small geographic areas.
“Overall, our results may suggest that the physical food environment may not play as strong a role in characterizing the risk of type 2 diabetes among children and that other factors such as genetics, health behaviors, environmental exposures, or family influences may play more important roles.”
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation. No conflicts of interest were declared.
SOURCE: Lee DC et al. J Endocr Soc. 2018. Apr 17. doi: 10.1210/js.2018-00001.
Areas with a high density of fast food outlets are associated with a greater prevalence of type 1 diabetes but not type 2 diabetes, according to new research.
These findings come from an analysis of emergency claims data for 5 million adults and 1.6 million children in New York who visited an emergency department at least once during 2009-2013. Researchers also looked at sociodemographic data for the area from community surveys and used local authorities’ inspection data to characterize local restaurant and retail food environments.
But when the analysis was adjusted to account for a range of factors, including age, sex, ethnicity, household income, and employment rates, the association between fast food swamps and diabetes was significant for pediatric type 1 diabetes only.
“Given the rising prevalence of type 1 diabetes, there has been increasing belief that certain environmental influences are contributing sharply to these increases,” wrote David C. Lee, MD, New York University Langone Health, and his coauthors. “There is some emerging literature which suggests that pregnant women in adverse food environments may have a higher likelihood of gestational diabetes, which some believe may affect health outcomes in their offspring.”
The study also failed to find an influence of retail food swamps – areas with more bodegas or small convenience stores within a 1-mile radius – on the prevalence of either type 1 or type 2 diabetes, in either adults or children. When researchers extended this to a 2-mile radius, they did find a significantly higher prevalence of pediatric type 1 diabetes associated with retail food swamps but a significantly lower prevalence of adult type 1 diabetes.
“This result may suggest that the retail food environment does not have a strong association with local diabetes prevalence or may be due to how we measured the retail food environment,” they wrote.
In general, the study found that the prevalence of adult and pediatric type 1 diabetes was significantly lower in most black neighborhoods, while the prevalence of adult type 1 diabetes was significantly lower in most Hispanic neighborhoods. Higher-income neighborhoods showed a significantly higher prevalence of pediatric type 1 diabetes.
The prevalence of type 2 diabetes in adults was significantly higher in low-income neighborhoods and those with more elderly residents, while the highest rates of pediatric type 2 diabetes were found in black neighborhoods.
The authors commented that they were surprised that their data did not show a higher prevalence of adult type 2 diabetes in black neighborhoods.
“In our multivariate analysis, older age and lower income were the only demographic or socioeconomic factors associated with higher adult type 2 diabetes prevalence,” they wrote.
Their use of ED surveillance data may have skewed the findings toward individuals more likely to visit those departments, namely Medicaid patients. But they suggested this would be balanced by the fact that the analysis was based on small geographic areas.
“Overall, our results may suggest that the physical food environment may not play as strong a role in characterizing the risk of type 2 diabetes among children and that other factors such as genetics, health behaviors, environmental exposures, or family influences may play more important roles.”
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation. No conflicts of interest were declared.
SOURCE: Lee DC et al. J Endocr Soc. 2018. Apr 17. doi: 10.1210/js.2018-00001.
FROM JOURNAL OF THE ENDOCRINE SOCIETY
Key clinical point: Neighborhoods with higher numbers of fast food restaurants are linked to a higher prevalence of type 1, not type 2, diabetes.
Major finding: Fast food swamps are associated with a higher prevalence of pediatric type 1 diabetes.
Study details: Retrospective analysis of emergency claims data for 5 million adults and 1.6 million children.
Disclosures: The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation. No conflicts of interest were declared.
Source: Lee DC et al. J Endocr Soc. 2018. Apr 17. doi: 10.1210/js.2018-00001.
Nivolumab plus ipilimumab boosts PFS in advanced NSCLC with high tumor mutational burden
CHICAGO – The combination of nivolumab plus ipilimumab prolonged progression-free survival (PFS), in comparison with platinum based chemotherapy, as initial treatment for advanced non–small cell lung cancer (NSCLC) patients with a high tumor mutation burden (TMB), regardless of PDL-1 status, according to the first analysis of Checkmate 227.
Median PFS was 7.2 months for patients receiving the immunotherapy combination (95% confidence interval, 5.5-13.2) versus 5.5 months (95% CI, 4.4-5.8) for those receiving platinum-based chemotherapy (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41-0.81; P less than .001).
The trial results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection, Matthew D. Hellmann, MD, said at the annual meeting of the American Association for Cancer Research.
“Checkmate 227 is the pivotal phase 3 study to validate TMB as an important and independent biomarker to be routinely tested in treatment-naive advanced NSCLC,” he said.
Overall survival data with the combination versus chemotherapy was “encouraging” but not yet complete in patients with high TMB, Dr. Hellmann said.
Results from this first analysis (part 1) of Checkmate 227, a multipart trial, were simultaneously published in the New England Journal of Medicine.
The trial was designed prior to emerging data about TMB. The study was later amended prior to initial analysis to include a second coprimary endpoint evaluating PFS with nivolumab plus ipilimumab versus chemotherapy among patients with a tumor mutational burden of at least 10 mutations per megabase (mut/Mb), irrespective of PD-L1 expression level.
For part 1 of the trial, patients were randomized 1:1:1 to nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks; histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles; and nivolumab 240 mg every 2 weeks or nivolumab 360 mg plus histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles, followed by nivolumab monotherapy.
Of all randomized patients in part 1 (n=1,739), 1,004 (58%) were evaluable for TMB analyses. Of all TMB-evaluable patients, 444 (44%) had TMB greater than or equal to 10 mut/Mb, including 139 patients randomized to nivolumab plus ipilimumab and 160 patients randomized to chemotherapy. TMB was assessed using the validated assay, FoundationOne CDx.
One-year PFS was higher with nivolumab plus ipilimumab than with chemotherapy among all randomized patients in part 1 (30.9% vs. 17.0%; HR for disease progression or death, 0.83; 95% CI, 0.72-0.96).
The PFS was significantly prolonged with the combination, compared with chemotherapy among patients with a high TMB; the 1-year PFS rate was 42.6% versus 13.2%, respectively, and the median PFS was 7.2 months (95% CI, 5.5-13.2) versus 5.5 months (95% CI, 4.4-5.8) respectively (HR for disease progression or death, 0.58; 97.5% CI, 0.41-0.81; P less than .001). In a subgroup analysis, PFS was longer with nivolumab plus ipilimumab versus chemotherapy for patients with a programmed death ligand 1 expression level of at least 1% and those with a level of less than 1%, reported Dr. Hellmann of Memorial Sloan Kettering Cancer Center, New York.
Safety was manageable and consistent with previous reports of nivolumab plus low-dose ipilimumab in NSCLC. Grade 3-4 treatment-related adverse events with the combination were skin reactions (34%), endocrine (23%), gastrointestinal (18%), hepatic (15%), pulmonary (8%), hypersensitivity (4%), and renal (4%) events. Overall, treatment-related deaths occurred in 1% of patients treated in both the combination and chemotherapy arms.
Results from Checkmate 227 may introduce two new standards of care for the first-line treatment of NSCLC, Dr. Hellmann said. The immunotherapy combination is introduced as a new option for the first-line treatment of NSCLC with a high TMB, sparing first-line chemotherapy, and it validates TMB as an “important and independent biomarker to be routinely tested in treatment-naive, advanced NSCLC,” he concluded.
Dr. Hellmann disclosed relationships with Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, Janssen, Mirati, and Shattuck Labs.
SOURCE: Hellmann MD et al. AACR Annual Meeting, Abstract CT077.
CHICAGO – The combination of nivolumab plus ipilimumab prolonged progression-free survival (PFS), in comparison with platinum based chemotherapy, as initial treatment for advanced non–small cell lung cancer (NSCLC) patients with a high tumor mutation burden (TMB), regardless of PDL-1 status, according to the first analysis of Checkmate 227.
Median PFS was 7.2 months for patients receiving the immunotherapy combination (95% confidence interval, 5.5-13.2) versus 5.5 months (95% CI, 4.4-5.8) for those receiving platinum-based chemotherapy (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41-0.81; P less than .001).
The trial results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection, Matthew D. Hellmann, MD, said at the annual meeting of the American Association for Cancer Research.
“Checkmate 227 is the pivotal phase 3 study to validate TMB as an important and independent biomarker to be routinely tested in treatment-naive advanced NSCLC,” he said.
Overall survival data with the combination versus chemotherapy was “encouraging” but not yet complete in patients with high TMB, Dr. Hellmann said.
Results from this first analysis (part 1) of Checkmate 227, a multipart trial, were simultaneously published in the New England Journal of Medicine.
The trial was designed prior to emerging data about TMB. The study was later amended prior to initial analysis to include a second coprimary endpoint evaluating PFS with nivolumab plus ipilimumab versus chemotherapy among patients with a tumor mutational burden of at least 10 mutations per megabase (mut/Mb), irrespective of PD-L1 expression level.
For part 1 of the trial, patients were randomized 1:1:1 to nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks; histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles; and nivolumab 240 mg every 2 weeks or nivolumab 360 mg plus histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles, followed by nivolumab monotherapy.
Of all randomized patients in part 1 (n=1,739), 1,004 (58%) were evaluable for TMB analyses. Of all TMB-evaluable patients, 444 (44%) had TMB greater than or equal to 10 mut/Mb, including 139 patients randomized to nivolumab plus ipilimumab and 160 patients randomized to chemotherapy. TMB was assessed using the validated assay, FoundationOne CDx.
One-year PFS was higher with nivolumab plus ipilimumab than with chemotherapy among all randomized patients in part 1 (30.9% vs. 17.0%; HR for disease progression or death, 0.83; 95% CI, 0.72-0.96).
The PFS was significantly prolonged with the combination, compared with chemotherapy among patients with a high TMB; the 1-year PFS rate was 42.6% versus 13.2%, respectively, and the median PFS was 7.2 months (95% CI, 5.5-13.2) versus 5.5 months (95% CI, 4.4-5.8) respectively (HR for disease progression or death, 0.58; 97.5% CI, 0.41-0.81; P less than .001). In a subgroup analysis, PFS was longer with nivolumab plus ipilimumab versus chemotherapy for patients with a programmed death ligand 1 expression level of at least 1% and those with a level of less than 1%, reported Dr. Hellmann of Memorial Sloan Kettering Cancer Center, New York.
Safety was manageable and consistent with previous reports of nivolumab plus low-dose ipilimumab in NSCLC. Grade 3-4 treatment-related adverse events with the combination were skin reactions (34%), endocrine (23%), gastrointestinal (18%), hepatic (15%), pulmonary (8%), hypersensitivity (4%), and renal (4%) events. Overall, treatment-related deaths occurred in 1% of patients treated in both the combination and chemotherapy arms.
Results from Checkmate 227 may introduce two new standards of care for the first-line treatment of NSCLC, Dr. Hellmann said. The immunotherapy combination is introduced as a new option for the first-line treatment of NSCLC with a high TMB, sparing first-line chemotherapy, and it validates TMB as an “important and independent biomarker to be routinely tested in treatment-naive, advanced NSCLC,” he concluded.
Dr. Hellmann disclosed relationships with Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, Janssen, Mirati, and Shattuck Labs.
SOURCE: Hellmann MD et al. AACR Annual Meeting, Abstract CT077.
CHICAGO – The combination of nivolumab plus ipilimumab prolonged progression-free survival (PFS), in comparison with platinum based chemotherapy, as initial treatment for advanced non–small cell lung cancer (NSCLC) patients with a high tumor mutation burden (TMB), regardless of PDL-1 status, according to the first analysis of Checkmate 227.
Median PFS was 7.2 months for patients receiving the immunotherapy combination (95% confidence interval, 5.5-13.2) versus 5.5 months (95% CI, 4.4-5.8) for those receiving platinum-based chemotherapy (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41-0.81; P less than .001).
The trial results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection, Matthew D. Hellmann, MD, said at the annual meeting of the American Association for Cancer Research.
“Checkmate 227 is the pivotal phase 3 study to validate TMB as an important and independent biomarker to be routinely tested in treatment-naive advanced NSCLC,” he said.
Overall survival data with the combination versus chemotherapy was “encouraging” but not yet complete in patients with high TMB, Dr. Hellmann said.
Results from this first analysis (part 1) of Checkmate 227, a multipart trial, were simultaneously published in the New England Journal of Medicine.
The trial was designed prior to emerging data about TMB. The study was later amended prior to initial analysis to include a second coprimary endpoint evaluating PFS with nivolumab plus ipilimumab versus chemotherapy among patients with a tumor mutational burden of at least 10 mutations per megabase (mut/Mb), irrespective of PD-L1 expression level.
For part 1 of the trial, patients were randomized 1:1:1 to nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks; histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles; and nivolumab 240 mg every 2 weeks or nivolumab 360 mg plus histology-based platinum-doublet chemotherapy every 3 weeks for up to four cycles, followed by nivolumab monotherapy.
Of all randomized patients in part 1 (n=1,739), 1,004 (58%) were evaluable for TMB analyses. Of all TMB-evaluable patients, 444 (44%) had TMB greater than or equal to 10 mut/Mb, including 139 patients randomized to nivolumab plus ipilimumab and 160 patients randomized to chemotherapy. TMB was assessed using the validated assay, FoundationOne CDx.
One-year PFS was higher with nivolumab plus ipilimumab than with chemotherapy among all randomized patients in part 1 (30.9% vs. 17.0%; HR for disease progression or death, 0.83; 95% CI, 0.72-0.96).
The PFS was significantly prolonged with the combination, compared with chemotherapy among patients with a high TMB; the 1-year PFS rate was 42.6% versus 13.2%, respectively, and the median PFS was 7.2 months (95% CI, 5.5-13.2) versus 5.5 months (95% CI, 4.4-5.8) respectively (HR for disease progression or death, 0.58; 97.5% CI, 0.41-0.81; P less than .001). In a subgroup analysis, PFS was longer with nivolumab plus ipilimumab versus chemotherapy for patients with a programmed death ligand 1 expression level of at least 1% and those with a level of less than 1%, reported Dr. Hellmann of Memorial Sloan Kettering Cancer Center, New York.
Safety was manageable and consistent with previous reports of nivolumab plus low-dose ipilimumab in NSCLC. Grade 3-4 treatment-related adverse events with the combination were skin reactions (34%), endocrine (23%), gastrointestinal (18%), hepatic (15%), pulmonary (8%), hypersensitivity (4%), and renal (4%) events. Overall, treatment-related deaths occurred in 1% of patients treated in both the combination and chemotherapy arms.
Results from Checkmate 227 may introduce two new standards of care for the first-line treatment of NSCLC, Dr. Hellmann said. The immunotherapy combination is introduced as a new option for the first-line treatment of NSCLC with a high TMB, sparing first-line chemotherapy, and it validates TMB as an “important and independent biomarker to be routinely tested in treatment-naive, advanced NSCLC,” he concluded.
Dr. Hellmann disclosed relationships with Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, Janssen, Mirati, and Shattuck Labs.
SOURCE: Hellmann MD et al. AACR Annual Meeting, Abstract CT077.
REPORTING FROM THE AACR ANNUAL MEETING
Key clinical point: PFS was prolonged with the immunotherapy combination of nivolumab plus low-dose ipilimumab versus chemotherapy in first-line advanced NSCLC patients with high tumor mutational burden, independent of PD-L1 expression or tumor histology.
Major finding: Median progression-free survival was 7.2 months (95% CI, 5.5-13.2) for the immunotherapy combination versus 5.5 months (95% CI, 4.4-5.8) for chemotherapy (HR, 0.58; 97.5% CI, 0.41-0.81; P less than .001).
Study details: CheckMate-227 is a multipart open-label phase 3 trial evaluating nivolumab-based combinations versus platinum-doublet chemotherapy in patients with first-line advanced non–small cell lung cancer across nonsquamous and squamous tumor histology.
Disclosures: Dr. Hellmann disclosed relationships with Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, Janssen, Mirati, and Shattuck Labs.
Source: Hellmann MD et al. AACR Annual Meeting, Abstract CT077.
Clopidogrel flunks platelet reactivity control test in TAVI
WASHINGTON – For antithrombotic therapy after transcatheter aortic valve implantation (TAVI), ticagrelor plus aspirin may be a better strategy than clopidogrel plus aspirin even though the latter combination is guideline recommended, according to a late-breaking, randomized study presented at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.
Unlike the ticagrelor regimen, which did deliver the goal antiplatelet effect for all 3 months of the study, “clopidogrel did not achieve adequate platelet inhibition before or after TAVI in most patients,” reported Victor A. Jimenez Diaz, MD, a cardiologist at University Hospital, Vigo, Spain.
The current American Heart Association/American College of Cardiology guidelines label the clopidogrel/aspirin combination for the first 6 months after TAVI “reasonable,” but Dr. Jimenez Diaz said that the value of this combination over other antiplatelet strategies has not been supported by a randomized clinical trial. The known variability in response to clopidogrel is among the reasons such data are needed.
Thrombotic and hemorrhagic complications are frequent after TAVI, making choice of antithrombotic treatment an important consideration for improving outcomes, according to Dr. Jimenez Diaz. The aim of the REAC TAVI trial was to evaluate whether ticagrelor provides a more consistent antiplatelet effect than clopidogrel for TAVI patients, which was undertaken at seven participating centers in Spain.
A total of 65 candidates for TAVI were enrolled in this study. The key exclusion criterion was chronic oral anticoagulation therapy. In a baseline assessment, patients in the study, all of whom were on 75 mg clopidogrel plus aspirin, were evaluated for high on-treatment platelet reactivity (HTPR), defined as a score of at least 208 platelet reaction units (PRU) on a standard assay.
The 46 (71%) patients found to have HTPR were randomized to 90 mg ticagrelor twice daily plus aspirin or to remain on the clopidogrel/aspirin combination. Unlike those with HTPR, in whom the mean PRU was 274 units, all of the patients without HTPR, who had a mean PRU of 134 units, remained on the baseline dual antiplatelet therapy. The study was open label.
The primary endpoint was adequate platelet antiaggregation, defined as absence of HTPR (less than 208 PRU), which was greater in the ticagrelor-treated group than the clopidogrel-treated group at 6 hours (91% vs. 4%), 5 days (100% vs. 10%), and 3 months (100% vs. 21%). In the patients without HTPR, the proportion with adequate platelet antiaggregation at these three time points were 73%, 64%, and 78%, respectively.
“The net difference in the randomized arms over the course of the study was 79%,” reported Dr. Jimenez Diaz, emphasizing that the study verified the hypothesis that ticagrelor would provide a more consistent antiplatelet effect than clopidogrel.
Although in-hospital bleeding complications were numerically higher in the clopidogrel-treated group (25% vs. 4%), this difference did not reach significance, and there were no significant differences in bleeding complications at any other time points or overall. There were two deaths in the clopidogrel-treated group, two deaths in the group without baseline HTPR, but no deaths in the ticagrelor-treated group.
While acknowledging that this study was small and not powered to show a difference in clinical events, Dr. Jimenez Diaz said it is important to emphasize that two-thirds of patients had HTPR at baseline. The high rate of HTPR among TAVI patients on clopidogrel and aspirin at baseline was identified as an important message from this study. However, a study is now needed to determine whether a ticagrelor strategy improves clinical outcomes when compared with a clopidogrel strategy.
A panel of experts at the CRT late-breaker session where these results were presented offered mixed reactions. While Jeffrey Popma, MD, director of interventional cardiology at Beth Israel Deaconess Hospital, Boston, called the results both “intriguing” and “provocative,” Ron Waksman, MD, associate director of the division of cardiology at the Medstar Health Institute, Washington, offered a note of caution, commenting that this application of ticagrelor “is off label, and then you would have to be concerned about the bleeding risk.”
However, all agreed that the optimal antithrombotic therapy for TAVI remains poorly defined and that randomized trials are needed to explore this issue.
This investigator-initiated study had no commercial sponsor. Dr. Jimenez Diaz reported no relevant financial relationships.
SOURCE: Jimenez Diaz VA. CRT 2018, Abstract LBT-10.
WASHINGTON – For antithrombotic therapy after transcatheter aortic valve implantation (TAVI), ticagrelor plus aspirin may be a better strategy than clopidogrel plus aspirin even though the latter combination is guideline recommended, according to a late-breaking, randomized study presented at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.
Unlike the ticagrelor regimen, which did deliver the goal antiplatelet effect for all 3 months of the study, “clopidogrel did not achieve adequate platelet inhibition before or after TAVI in most patients,” reported Victor A. Jimenez Diaz, MD, a cardiologist at University Hospital, Vigo, Spain.
The current American Heart Association/American College of Cardiology guidelines label the clopidogrel/aspirin combination for the first 6 months after TAVI “reasonable,” but Dr. Jimenez Diaz said that the value of this combination over other antiplatelet strategies has not been supported by a randomized clinical trial. The known variability in response to clopidogrel is among the reasons such data are needed.
Thrombotic and hemorrhagic complications are frequent after TAVI, making choice of antithrombotic treatment an important consideration for improving outcomes, according to Dr. Jimenez Diaz. The aim of the REAC TAVI trial was to evaluate whether ticagrelor provides a more consistent antiplatelet effect than clopidogrel for TAVI patients, which was undertaken at seven participating centers in Spain.
A total of 65 candidates for TAVI were enrolled in this study. The key exclusion criterion was chronic oral anticoagulation therapy. In a baseline assessment, patients in the study, all of whom were on 75 mg clopidogrel plus aspirin, were evaluated for high on-treatment platelet reactivity (HTPR), defined as a score of at least 208 platelet reaction units (PRU) on a standard assay.
The 46 (71%) patients found to have HTPR were randomized to 90 mg ticagrelor twice daily plus aspirin or to remain on the clopidogrel/aspirin combination. Unlike those with HTPR, in whom the mean PRU was 274 units, all of the patients without HTPR, who had a mean PRU of 134 units, remained on the baseline dual antiplatelet therapy. The study was open label.
The primary endpoint was adequate platelet antiaggregation, defined as absence of HTPR (less than 208 PRU), which was greater in the ticagrelor-treated group than the clopidogrel-treated group at 6 hours (91% vs. 4%), 5 days (100% vs. 10%), and 3 months (100% vs. 21%). In the patients without HTPR, the proportion with adequate platelet antiaggregation at these three time points were 73%, 64%, and 78%, respectively.
“The net difference in the randomized arms over the course of the study was 79%,” reported Dr. Jimenez Diaz, emphasizing that the study verified the hypothesis that ticagrelor would provide a more consistent antiplatelet effect than clopidogrel.
Although in-hospital bleeding complications were numerically higher in the clopidogrel-treated group (25% vs. 4%), this difference did not reach significance, and there were no significant differences in bleeding complications at any other time points or overall. There were two deaths in the clopidogrel-treated group, two deaths in the group without baseline HTPR, but no deaths in the ticagrelor-treated group.
While acknowledging that this study was small and not powered to show a difference in clinical events, Dr. Jimenez Diaz said it is important to emphasize that two-thirds of patients had HTPR at baseline. The high rate of HTPR among TAVI patients on clopidogrel and aspirin at baseline was identified as an important message from this study. However, a study is now needed to determine whether a ticagrelor strategy improves clinical outcomes when compared with a clopidogrel strategy.
A panel of experts at the CRT late-breaker session where these results were presented offered mixed reactions. While Jeffrey Popma, MD, director of interventional cardiology at Beth Israel Deaconess Hospital, Boston, called the results both “intriguing” and “provocative,” Ron Waksman, MD, associate director of the division of cardiology at the Medstar Health Institute, Washington, offered a note of caution, commenting that this application of ticagrelor “is off label, and then you would have to be concerned about the bleeding risk.”
However, all agreed that the optimal antithrombotic therapy for TAVI remains poorly defined and that randomized trials are needed to explore this issue.
This investigator-initiated study had no commercial sponsor. Dr. Jimenez Diaz reported no relevant financial relationships.
SOURCE: Jimenez Diaz VA. CRT 2018, Abstract LBT-10.
WASHINGTON – For antithrombotic therapy after transcatheter aortic valve implantation (TAVI), ticagrelor plus aspirin may be a better strategy than clopidogrel plus aspirin even though the latter combination is guideline recommended, according to a late-breaking, randomized study presented at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.
Unlike the ticagrelor regimen, which did deliver the goal antiplatelet effect for all 3 months of the study, “clopidogrel did not achieve adequate platelet inhibition before or after TAVI in most patients,” reported Victor A. Jimenez Diaz, MD, a cardiologist at University Hospital, Vigo, Spain.
The current American Heart Association/American College of Cardiology guidelines label the clopidogrel/aspirin combination for the first 6 months after TAVI “reasonable,” but Dr. Jimenez Diaz said that the value of this combination over other antiplatelet strategies has not been supported by a randomized clinical trial. The known variability in response to clopidogrel is among the reasons such data are needed.
Thrombotic and hemorrhagic complications are frequent after TAVI, making choice of antithrombotic treatment an important consideration for improving outcomes, according to Dr. Jimenez Diaz. The aim of the REAC TAVI trial was to evaluate whether ticagrelor provides a more consistent antiplatelet effect than clopidogrel for TAVI patients, which was undertaken at seven participating centers in Spain.
A total of 65 candidates for TAVI were enrolled in this study. The key exclusion criterion was chronic oral anticoagulation therapy. In a baseline assessment, patients in the study, all of whom were on 75 mg clopidogrel plus aspirin, were evaluated for high on-treatment platelet reactivity (HTPR), defined as a score of at least 208 platelet reaction units (PRU) on a standard assay.
The 46 (71%) patients found to have HTPR were randomized to 90 mg ticagrelor twice daily plus aspirin or to remain on the clopidogrel/aspirin combination. Unlike those with HTPR, in whom the mean PRU was 274 units, all of the patients without HTPR, who had a mean PRU of 134 units, remained on the baseline dual antiplatelet therapy. The study was open label.
The primary endpoint was adequate platelet antiaggregation, defined as absence of HTPR (less than 208 PRU), which was greater in the ticagrelor-treated group than the clopidogrel-treated group at 6 hours (91% vs. 4%), 5 days (100% vs. 10%), and 3 months (100% vs. 21%). In the patients without HTPR, the proportion with adequate platelet antiaggregation at these three time points were 73%, 64%, and 78%, respectively.
“The net difference in the randomized arms over the course of the study was 79%,” reported Dr. Jimenez Diaz, emphasizing that the study verified the hypothesis that ticagrelor would provide a more consistent antiplatelet effect than clopidogrel.
Although in-hospital bleeding complications were numerically higher in the clopidogrel-treated group (25% vs. 4%), this difference did not reach significance, and there were no significant differences in bleeding complications at any other time points or overall. There were two deaths in the clopidogrel-treated group, two deaths in the group without baseline HTPR, but no deaths in the ticagrelor-treated group.
While acknowledging that this study was small and not powered to show a difference in clinical events, Dr. Jimenez Diaz said it is important to emphasize that two-thirds of patients had HTPR at baseline. The high rate of HTPR among TAVI patients on clopidogrel and aspirin at baseline was identified as an important message from this study. However, a study is now needed to determine whether a ticagrelor strategy improves clinical outcomes when compared with a clopidogrel strategy.
A panel of experts at the CRT late-breaker session where these results were presented offered mixed reactions. While Jeffrey Popma, MD, director of interventional cardiology at Beth Israel Deaconess Hospital, Boston, called the results both “intriguing” and “provocative,” Ron Waksman, MD, associate director of the division of cardiology at the Medstar Health Institute, Washington, offered a note of caution, commenting that this application of ticagrelor “is off label, and then you would have to be concerned about the bleeding risk.”
However, all agreed that the optimal antithrombotic therapy for TAVI remains poorly defined and that randomized trials are needed to explore this issue.
This investigator-initiated study had no commercial sponsor. Dr. Jimenez Diaz reported no relevant financial relationships.
SOURCE: Jimenez Diaz VA. CRT 2018, Abstract LBT-10.
REPORTING FROM CRT 2018
Key clinical point: For platelet reactivity after transcatheter aortic valve implantation (TAVI), ticagrelor is more effective than clopidogrel.
Major finding:
Study details: A multicenter, randomized trial with 65 patients.
Disclosures: This investigator-initiated study had no commercial sponsor. Dr. Jimenez Diaz reported no relevant financial relationships.
Source: Jimenez Diaz VA. CRT 2018, Abstract LBT-10.
Don’t use cannabis to treat OSA, AASM recommends
, according to a position statement published in the Journal of Clinical Sleep Medicine’s April issue.
In the statement, the professional society recommends that state legislators, regulators, and health departments exclude obstructive sleep apnea (OSA) as an indication for medical cannabis programs.
The “unreliable delivery methods and insufficient evidence of treatment effectiveness, tolerability, and safety” of medical cannabis and its synthetic extracts are among the reasons the AASM gave for making its recommendations. “Further research is needed to better understand the mechanistic actions of medical cannabis and its synthetic extracts, the long-term role of these synthetic extracts on OSA treatment, and harms and benefits,” the AASM concluded in its statement, authored by Kannan Ramar, MD, and other members of a panel of experts on sleep medicine.
Dronabinol is the only cannabis product that has been tested on patients with OSA for the treatment of this disorder. While some synthetic cannabis products are approved by the Food and Drug Administration for other medical indications, the synthetic-based cannabis product dronabinol has not received FDA approval for the treatment of OSA.
Researchers have examined dronabinol’s use for treating OSA in small pilot and proof-of-concept studies and most patients in these studies reported experiencing treatment-related side effects, such as somnolence, wrote Dr. Ramar, of the division of pulmonary and critical care medicine at the Center for Sleep Medicine, Mayo Clinic, Rochester Minn., and his colleagues.
These trials involved patients having taken dronabinol pills in strengths ranging from 2.5 mg to 10 mg. One such study (Front Psychiatry. 2013 Jan 22. doi: 10.3389/fpsyt.2013.00001), authored by Bharati Prasad of the University of Illinois, Chicago, and colleagues, showed a significant improvement in apnea-hypopnea index (AHI) of 32%, after 17 patients used dronabinol for 3 weeks, when compared with baseline AHIs (–14.1; P = .007).
A placebo-controlled randomized study of 73 adults with moderate or severe OSA similarly found a 33% decline in AHI in patients following 6 weeks of treatment with 10-mg doses of dronabinol (Sleep. 2018 Jan 1. doi: 10.1093/sleep/zsx184).
In the placebo-controlled study, 73 patients were randomized to receive 2.5 mg of dronabinol or 10 mg of dronabinol daily for up to 6 weeks, or placebo. At the end of treatment, researchers saw significant increases in the AHI among the patients on placebo, while those who received dronabinol showed decreases in the number of apnea and hypopnea events per hour. Patients given the 2.5-mg dose of dronabinol had a mean decrease of 10.7 events per hour, and those on the 10-mg dose had a mean decrease of 12.9 events per hour compared with placebo. The difference between the placebo and treatment arms was significant for both dosages, and the AHI decreases were similar between the two dosages of dronabinol.
These effects were largely due to reductions in apnea events; the largest reduction was seen in the REM apnea index in patients treated with the 10-mg dose of dronabinol. However, there were few effects on the expression of hypopneas, except in the higher-dose group.
After adjustment for age, race, ethnicity, and baseline AHI, the increases seen in the placebo group were no longer significant, but the decreases from baseline seen in the treatment arms were greater. Dronabinol treatment also was associated with significant decreases, compared with placebo, in non-REM AHI and REM AHI.
Overall, nearly 90% of patients in this trial reported at least one adverse event, with the rates having not differed significantly between the treatment and placebo arms. The most frequently reported adverse events were “sleepiness/drowsiness” (n = 25; 8% of total adverse events reported), headache (n = 24; 8%), “nausea/vomiting” (n = 23; 8%), and “dizziness/lightheadedness” (n = 12; 4%). In addition, one patient experienced diarrhea and vomiting that required admission to a hospital, which was judged as possibly related to the study medication. There were six other withdrawals due to adverse events, including dizziness and vision changes, vertigo, ECG arrhythmias, and headache with dizziness and vomiting.
“Synthetic medical cannabis may have differential side effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA,” Dr. Ramar and his associates wrote.
, according to a position statement published in the Journal of Clinical Sleep Medicine’s April issue.
In the statement, the professional society recommends that state legislators, regulators, and health departments exclude obstructive sleep apnea (OSA) as an indication for medical cannabis programs.
The “unreliable delivery methods and insufficient evidence of treatment effectiveness, tolerability, and safety” of medical cannabis and its synthetic extracts are among the reasons the AASM gave for making its recommendations. “Further research is needed to better understand the mechanistic actions of medical cannabis and its synthetic extracts, the long-term role of these synthetic extracts on OSA treatment, and harms and benefits,” the AASM concluded in its statement, authored by Kannan Ramar, MD, and other members of a panel of experts on sleep medicine.
Dronabinol is the only cannabis product that has been tested on patients with OSA for the treatment of this disorder. While some synthetic cannabis products are approved by the Food and Drug Administration for other medical indications, the synthetic-based cannabis product dronabinol has not received FDA approval for the treatment of OSA.
Researchers have examined dronabinol’s use for treating OSA in small pilot and proof-of-concept studies and most patients in these studies reported experiencing treatment-related side effects, such as somnolence, wrote Dr. Ramar, of the division of pulmonary and critical care medicine at the Center for Sleep Medicine, Mayo Clinic, Rochester Minn., and his colleagues.
These trials involved patients having taken dronabinol pills in strengths ranging from 2.5 mg to 10 mg. One such study (Front Psychiatry. 2013 Jan 22. doi: 10.3389/fpsyt.2013.00001), authored by Bharati Prasad of the University of Illinois, Chicago, and colleagues, showed a significant improvement in apnea-hypopnea index (AHI) of 32%, after 17 patients used dronabinol for 3 weeks, when compared with baseline AHIs (–14.1; P = .007).
A placebo-controlled randomized study of 73 adults with moderate or severe OSA similarly found a 33% decline in AHI in patients following 6 weeks of treatment with 10-mg doses of dronabinol (Sleep. 2018 Jan 1. doi: 10.1093/sleep/zsx184).
In the placebo-controlled study, 73 patients were randomized to receive 2.5 mg of dronabinol or 10 mg of dronabinol daily for up to 6 weeks, or placebo. At the end of treatment, researchers saw significant increases in the AHI among the patients on placebo, while those who received dronabinol showed decreases in the number of apnea and hypopnea events per hour. Patients given the 2.5-mg dose of dronabinol had a mean decrease of 10.7 events per hour, and those on the 10-mg dose had a mean decrease of 12.9 events per hour compared with placebo. The difference between the placebo and treatment arms was significant for both dosages, and the AHI decreases were similar between the two dosages of dronabinol.
These effects were largely due to reductions in apnea events; the largest reduction was seen in the REM apnea index in patients treated with the 10-mg dose of dronabinol. However, there were few effects on the expression of hypopneas, except in the higher-dose group.
After adjustment for age, race, ethnicity, and baseline AHI, the increases seen in the placebo group were no longer significant, but the decreases from baseline seen in the treatment arms were greater. Dronabinol treatment also was associated with significant decreases, compared with placebo, in non-REM AHI and REM AHI.
Overall, nearly 90% of patients in this trial reported at least one adverse event, with the rates having not differed significantly between the treatment and placebo arms. The most frequently reported adverse events were “sleepiness/drowsiness” (n = 25; 8% of total adverse events reported), headache (n = 24; 8%), “nausea/vomiting” (n = 23; 8%), and “dizziness/lightheadedness” (n = 12; 4%). In addition, one patient experienced diarrhea and vomiting that required admission to a hospital, which was judged as possibly related to the study medication. There were six other withdrawals due to adverse events, including dizziness and vision changes, vertigo, ECG arrhythmias, and headache with dizziness and vomiting.
“Synthetic medical cannabis may have differential side effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA,” Dr. Ramar and his associates wrote.
, according to a position statement published in the Journal of Clinical Sleep Medicine’s April issue.
In the statement, the professional society recommends that state legislators, regulators, and health departments exclude obstructive sleep apnea (OSA) as an indication for medical cannabis programs.
The “unreliable delivery methods and insufficient evidence of treatment effectiveness, tolerability, and safety” of medical cannabis and its synthetic extracts are among the reasons the AASM gave for making its recommendations. “Further research is needed to better understand the mechanistic actions of medical cannabis and its synthetic extracts, the long-term role of these synthetic extracts on OSA treatment, and harms and benefits,” the AASM concluded in its statement, authored by Kannan Ramar, MD, and other members of a panel of experts on sleep medicine.
Dronabinol is the only cannabis product that has been tested on patients with OSA for the treatment of this disorder. While some synthetic cannabis products are approved by the Food and Drug Administration for other medical indications, the synthetic-based cannabis product dronabinol has not received FDA approval for the treatment of OSA.
Researchers have examined dronabinol’s use for treating OSA in small pilot and proof-of-concept studies and most patients in these studies reported experiencing treatment-related side effects, such as somnolence, wrote Dr. Ramar, of the division of pulmonary and critical care medicine at the Center for Sleep Medicine, Mayo Clinic, Rochester Minn., and his colleagues.
These trials involved patients having taken dronabinol pills in strengths ranging from 2.5 mg to 10 mg. One such study (Front Psychiatry. 2013 Jan 22. doi: 10.3389/fpsyt.2013.00001), authored by Bharati Prasad of the University of Illinois, Chicago, and colleagues, showed a significant improvement in apnea-hypopnea index (AHI) of 32%, after 17 patients used dronabinol for 3 weeks, when compared with baseline AHIs (–14.1; P = .007).
A placebo-controlled randomized study of 73 adults with moderate or severe OSA similarly found a 33% decline in AHI in patients following 6 weeks of treatment with 10-mg doses of dronabinol (Sleep. 2018 Jan 1. doi: 10.1093/sleep/zsx184).
In the placebo-controlled study, 73 patients were randomized to receive 2.5 mg of dronabinol or 10 mg of dronabinol daily for up to 6 weeks, or placebo. At the end of treatment, researchers saw significant increases in the AHI among the patients on placebo, while those who received dronabinol showed decreases in the number of apnea and hypopnea events per hour. Patients given the 2.5-mg dose of dronabinol had a mean decrease of 10.7 events per hour, and those on the 10-mg dose had a mean decrease of 12.9 events per hour compared with placebo. The difference between the placebo and treatment arms was significant for both dosages, and the AHI decreases were similar between the two dosages of dronabinol.
These effects were largely due to reductions in apnea events; the largest reduction was seen in the REM apnea index in patients treated with the 10-mg dose of dronabinol. However, there were few effects on the expression of hypopneas, except in the higher-dose group.
After adjustment for age, race, ethnicity, and baseline AHI, the increases seen in the placebo group were no longer significant, but the decreases from baseline seen in the treatment arms were greater. Dronabinol treatment also was associated with significant decreases, compared with placebo, in non-REM AHI and REM AHI.
Overall, nearly 90% of patients in this trial reported at least one adverse event, with the rates having not differed significantly between the treatment and placebo arms. The most frequently reported adverse events were “sleepiness/drowsiness” (n = 25; 8% of total adverse events reported), headache (n = 24; 8%), “nausea/vomiting” (n = 23; 8%), and “dizziness/lightheadedness” (n = 12; 4%). In addition, one patient experienced diarrhea and vomiting that required admission to a hospital, which was judged as possibly related to the study medication. There were six other withdrawals due to adverse events, including dizziness and vision changes, vertigo, ECG arrhythmias, and headache with dizziness and vomiting.
“Synthetic medical cannabis may have differential side effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA,” Dr. Ramar and his associates wrote.
FROM THE JOURNAL OF CLINICAL SLEEP MEDICINE
MACE risk similar across arthritis subtypes
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Risk of major adverse cardiovascular events (MACE) was similar for patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis.
Major finding: For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. The older age of patients with rheumatoid arthritis explained most of their elevated absolute risk.
Study details: Population-based cohort study of 5,315 patients.
Disclosures: Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
Source: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Tips for performing complex laparoscopic gyn surgery
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VIDEO: Meta-analysis: Mortality, safety data may favor SGLT2 inhibitors in T2DM
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists were both associated with a lower mortality risk, compared with that seen with dipeptidyl peptidase–4 (DPP-4) inhibitors and in controls, in patients with type 2 diabetes, according to findings from a large network meta-analysis.
In addition, the GLP-1 agonists were associated with a higher risk of adverse events that led to study withdrawal, compared with SGLT2 inhibitors, according to the analysis conducted by Sean L. Zheng, BM BCh, of the department of endocrinology at the Imperial College Healthcare NHS Foundation Trust, London, and his coinvestigators.
“Of the 3 classes tested, SGLT2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse-event profile,” Dr. Zheng and his coinvestigators wrote in a report on the study published in JAMA.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Source: JAMA
For patients with type 2 diabetes who don’t achieve target glycemic control on metformin, Dr. Zheng and his coauthors noted, international guidelines recommend SGLT2 inhibitors or incretin-based treatments as a next step.
However, there has been little exploration of the relative clinical effectiveness of these drug classes, which has led to uncertainty about what treatment approach is optimal. “When no head-to-head trial exists, network meta-analysis can be used to estimate the effect,” the authors wrote.
To compare the efficacy of the drug classes in reducing mortality and cardiovascular outcomes, Dr. Zheng and his colleagues conducted a systematic review and meta-analysis of 236 randomized clinical trials including 176,310 participants.
The primary outcome of the study was all-cause mortality.
Both SGLT2 inhibitors and GLP-1 agonists were associated with significantly lower all-cause mortality than that seen in controls (placebo or no treatment), while DPP-4 inhibitors were not, investigators found in the meta-analysis.
For that endpoint, SGLT2 inhibitors had an absolute risk difference of –1.0%, with a hazard ratio of 0.80, and GLP-1 agonists had an absolute RD of –0.6% and an HR of 0.88. By contrast, DPP-4 inhibitors had an absolute RD of 0.1% and an HR of 1.02, according to the published report.
Moreover, when compared with DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists were associated with reduced all-cause mortality, with an absolute risk difference of –0.9% and –0.5%, respectively, they found.
SGLT2 inhibitors and GLP-1 agonists also were significantly associated with lower cardiovascular mortality than controls were, while SGLT2 inhibitors were significantly associated with lower heart failure event rates versus those seen controls, they also found.
Safety outcomes analysis showed that GLP-1 agonists, compared with SGLT2 inhibitors and DPP-4 inhibitors, had a higher risk of adverse events that led patients to withdraw from the study.
The DPP-4 inhibitors were associated with increased acute pancreatitis risk, according to the safety analysis. “SGLT2 inhibitors were associated with increased risk of genital infections but not urinary tract infections. There was a high degree of heterogeneity for lower-limb amputations driven by the significant increase in events with canagliflozin but neutral effects of empagliflozin,” they said.
“Careful treatment selection may be necessary to minimize these outcomes in at-risk patients,” Dr. Zheng and his coauthors concluded.
One author reported potential conflicts of interest with Roche Diabetes, Dexcom, Medtronics Diabetes, and others. Another was supported by a grant from the British Heart Foundation. No other conflicts were reported.
SOURCE: Zheng SL et al. JAMA. 2018;319(15):1580-91.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists were both associated with a lower mortality risk, compared with that seen with dipeptidyl peptidase–4 (DPP-4) inhibitors and in controls, in patients with type 2 diabetes, according to findings from a large network meta-analysis.
In addition, the GLP-1 agonists were associated with a higher risk of adverse events that led to study withdrawal, compared with SGLT2 inhibitors, according to the analysis conducted by Sean L. Zheng, BM BCh, of the department of endocrinology at the Imperial College Healthcare NHS Foundation Trust, London, and his coinvestigators.
“Of the 3 classes tested, SGLT2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse-event profile,” Dr. Zheng and his coinvestigators wrote in a report on the study published in JAMA.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Source: JAMA
For patients with type 2 diabetes who don’t achieve target glycemic control on metformin, Dr. Zheng and his coauthors noted, international guidelines recommend SGLT2 inhibitors or incretin-based treatments as a next step.
However, there has been little exploration of the relative clinical effectiveness of these drug classes, which has led to uncertainty about what treatment approach is optimal. “When no head-to-head trial exists, network meta-analysis can be used to estimate the effect,” the authors wrote.
To compare the efficacy of the drug classes in reducing mortality and cardiovascular outcomes, Dr. Zheng and his colleagues conducted a systematic review and meta-analysis of 236 randomized clinical trials including 176,310 participants.
The primary outcome of the study was all-cause mortality.
Both SGLT2 inhibitors and GLP-1 agonists were associated with significantly lower all-cause mortality than that seen in controls (placebo or no treatment), while DPP-4 inhibitors were not, investigators found in the meta-analysis.
For that endpoint, SGLT2 inhibitors had an absolute risk difference of –1.0%, with a hazard ratio of 0.80, and GLP-1 agonists had an absolute RD of –0.6% and an HR of 0.88. By contrast, DPP-4 inhibitors had an absolute RD of 0.1% and an HR of 1.02, according to the published report.
Moreover, when compared with DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists were associated with reduced all-cause mortality, with an absolute risk difference of –0.9% and –0.5%, respectively, they found.
SGLT2 inhibitors and GLP-1 agonists also were significantly associated with lower cardiovascular mortality than controls were, while SGLT2 inhibitors were significantly associated with lower heart failure event rates versus those seen controls, they also found.
Safety outcomes analysis showed that GLP-1 agonists, compared with SGLT2 inhibitors and DPP-4 inhibitors, had a higher risk of adverse events that led patients to withdraw from the study.
The DPP-4 inhibitors were associated with increased acute pancreatitis risk, according to the safety analysis. “SGLT2 inhibitors were associated with increased risk of genital infections but not urinary tract infections. There was a high degree of heterogeneity for lower-limb amputations driven by the significant increase in events with canagliflozin but neutral effects of empagliflozin,” they said.
“Careful treatment selection may be necessary to minimize these outcomes in at-risk patients,” Dr. Zheng and his coauthors concluded.
One author reported potential conflicts of interest with Roche Diabetes, Dexcom, Medtronics Diabetes, and others. Another was supported by a grant from the British Heart Foundation. No other conflicts were reported.
SOURCE: Zheng SL et al. JAMA. 2018;319(15):1580-91.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists were both associated with a lower mortality risk, compared with that seen with dipeptidyl peptidase–4 (DPP-4) inhibitors and in controls, in patients with type 2 diabetes, according to findings from a large network meta-analysis.
In addition, the GLP-1 agonists were associated with a higher risk of adverse events that led to study withdrawal, compared with SGLT2 inhibitors, according to the analysis conducted by Sean L. Zheng, BM BCh, of the department of endocrinology at the Imperial College Healthcare NHS Foundation Trust, London, and his coinvestigators.
“Of the 3 classes tested, SGLT2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse-event profile,” Dr. Zheng and his coinvestigators wrote in a report on the study published in JAMA.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Source: JAMA
For patients with type 2 diabetes who don’t achieve target glycemic control on metformin, Dr. Zheng and his coauthors noted, international guidelines recommend SGLT2 inhibitors or incretin-based treatments as a next step.
However, there has been little exploration of the relative clinical effectiveness of these drug classes, which has led to uncertainty about what treatment approach is optimal. “When no head-to-head trial exists, network meta-analysis can be used to estimate the effect,” the authors wrote.
To compare the efficacy of the drug classes in reducing mortality and cardiovascular outcomes, Dr. Zheng and his colleagues conducted a systematic review and meta-analysis of 236 randomized clinical trials including 176,310 participants.
The primary outcome of the study was all-cause mortality.
Both SGLT2 inhibitors and GLP-1 agonists were associated with significantly lower all-cause mortality than that seen in controls (placebo or no treatment), while DPP-4 inhibitors were not, investigators found in the meta-analysis.
For that endpoint, SGLT2 inhibitors had an absolute risk difference of –1.0%, with a hazard ratio of 0.80, and GLP-1 agonists had an absolute RD of –0.6% and an HR of 0.88. By contrast, DPP-4 inhibitors had an absolute RD of 0.1% and an HR of 1.02, according to the published report.
Moreover, when compared with DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists were associated with reduced all-cause mortality, with an absolute risk difference of –0.9% and –0.5%, respectively, they found.
SGLT2 inhibitors and GLP-1 agonists also were significantly associated with lower cardiovascular mortality than controls were, while SGLT2 inhibitors were significantly associated with lower heart failure event rates versus those seen controls, they also found.
Safety outcomes analysis showed that GLP-1 agonists, compared with SGLT2 inhibitors and DPP-4 inhibitors, had a higher risk of adverse events that led patients to withdraw from the study.
The DPP-4 inhibitors were associated with increased acute pancreatitis risk, according to the safety analysis. “SGLT2 inhibitors were associated with increased risk of genital infections but not urinary tract infections. There was a high degree of heterogeneity for lower-limb amputations driven by the significant increase in events with canagliflozin but neutral effects of empagliflozin,” they said.
“Careful treatment selection may be necessary to minimize these outcomes in at-risk patients,” Dr. Zheng and his coauthors concluded.
One author reported potential conflicts of interest with Roche Diabetes, Dexcom, Medtronics Diabetes, and others. Another was supported by a grant from the British Heart Foundation. No other conflicts were reported.
SOURCE: Zheng SL et al. JAMA. 2018;319(15):1580-91.
FROM JAMA
Key clinical point: that were either placebo or no treatment.
Major finding: When compared with DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists were both associated with reduced all-cause mortality, with an absolute risk difference of –0.9% and –0.5%, respectively.
Study details: A systematic review and meta-analysis of 236 randomized clinical trials including 176,310 participants.
Disclosures: One author reported potential conflicts of interest with Roche Diabetes, Dexcom, Medtronics Diabetes, and others. Another was supported by a grant from the British Heart Foundation. No other conflicts were reported.
Source: Zheng SL et al. JAMA. 2018;319(15):1580-91.
Dyspareunia Associated with Vulvovaginal Atrophy: Innovations in Counseling, Diagnosis, and Management
In the United States, there are approximately 64 million women who are postmenopausal. Of these women, it is estimated that 50%—or more than 32 million— have symptoms of vulvovaginal atrophy (VVA) and/or dyspareunia (painful sexual intercourse). These two conditions, along with several others, are components of the Genitourinary Syndrome of Menopause (GSM).
This CME-designated journal supplement is comprised of three articles that provide information and strategies regarding best practices as to patient counseling, diagnosis, and treatment of VVA, and its associated dyspareunia. The goal is to provide women’s health clinicians the knowledge and tools they need to optimize the care they provide to their menopausal patients.
Click here to read the supplement.
https://omniaeducation.com/dyspareunia/
An early version of this supplement distributed at the 2018 American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meetings incorrectly dated the second photo in Figure 9 on page S16 “8-4-2010”. This was later corrected to read “8-4-2011”.
In the United States, there are approximately 64 million women who are postmenopausal. Of these women, it is estimated that 50%—or more than 32 million— have symptoms of vulvovaginal atrophy (VVA) and/or dyspareunia (painful sexual intercourse). These two conditions, along with several others, are components of the Genitourinary Syndrome of Menopause (GSM).
This CME-designated journal supplement is comprised of three articles that provide information and strategies regarding best practices as to patient counseling, diagnosis, and treatment of VVA, and its associated dyspareunia. The goal is to provide women’s health clinicians the knowledge and tools they need to optimize the care they provide to their menopausal patients.
Click here to read the supplement.
https://omniaeducation.com/dyspareunia/
An early version of this supplement distributed at the 2018 American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meetings incorrectly dated the second photo in Figure 9 on page S16 “8-4-2010”. This was later corrected to read “8-4-2011”.
In the United States, there are approximately 64 million women who are postmenopausal. Of these women, it is estimated that 50%—or more than 32 million— have symptoms of vulvovaginal atrophy (VVA) and/or dyspareunia (painful sexual intercourse). These two conditions, along with several others, are components of the Genitourinary Syndrome of Menopause (GSM).
This CME-designated journal supplement is comprised of three articles that provide information and strategies regarding best practices as to patient counseling, diagnosis, and treatment of VVA, and its associated dyspareunia. The goal is to provide women’s health clinicians the knowledge and tools they need to optimize the care they provide to their menopausal patients.
Click here to read the supplement.
https://omniaeducation.com/dyspareunia/
An early version of this supplement distributed at the 2018 American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meetings incorrectly dated the second photo in Figure 9 on page S16 “8-4-2010”. This was later corrected to read “8-4-2011”.
