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Rituximab may be best choice for splenic MZL
For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.
Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.
The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.
Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.
“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.
Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.
However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.
“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.
Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.
Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.
Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.
The researchers reported having no relevant financial disclosures.
SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.
For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.
Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.
The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.
Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.
“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.
Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.
However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.
“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.
Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.
Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.
Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.
The researchers reported having no relevant financial disclosures.
SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.
For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.
Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.
The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.
Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.
“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.
Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.
However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.
“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.
Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.
Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.
Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.
The researchers reported having no relevant financial disclosures.
SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.
FROM BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
Key clinical point:
Major finding: Both splenectomy and rituximab are associated with high rates of 10-year overalls survival, but splenectomy has higher rates of surgical complications and infection.
Study details: Review article of 63 publications, mostly retrospective studies of marginal zone lymphoma.
Disclosures: The researchers reported having no relevant financial disclosures.
Source: Kalpadakis C et al. Best Pract Res Clin Haematol. 2017 Mar-Jun. doi:10.1016/j.beha.2017.10.011.
Tatiana Falcone, MD
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Andrew G. Herzog, MD
Thapanee Somboon, MD
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Justin Gover
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Surgery residents cite time challenges to robotics training
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
FROM THE AMERICAN JOURNAL OF SURGERY
Key clinical point: .
Major finding: 80% of surgical residents said that the length of time needed to complete a robotics curriculum was a barrier to doing so.
Data source: Survey of 97 general surgery residents conducted in 2014-2015 and 2016-2017.
Disclosures: The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
Source: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Optimal Duration of Antiplatelet Therapy Following Acute Coronary Syndrome
ADA guidelines embrace heart health
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
EXPERT ANALYSIS FROM DIABETES CARE
Applications due Feb. 1 for VAM Scholarships, Research Fellowship
SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarship to attend the 2018 Vascular Annual Meeting.
VAM will be held June 20 to 23, 2018, in Boston. (Plenaries are June 21-23 and exhibits are open June 21-22.) The Society for Vascular Surgery offers travel awards, including complimentary VAM registration, to be used toward the cost of travel, housing and meals.
Two awards are available, the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.
The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada.
Urge students you know with an interest in research to apply today.
SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarship to attend the 2018 Vascular Annual Meeting.
VAM will be held June 20 to 23, 2018, in Boston. (Plenaries are June 21-23 and exhibits are open June 21-22.) The Society for Vascular Surgery offers travel awards, including complimentary VAM registration, to be used toward the cost of travel, housing and meals.
Two awards are available, the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.
The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada.
Urge students you know with an interest in research to apply today.
SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarship to attend the 2018 Vascular Annual Meeting.
VAM will be held June 20 to 23, 2018, in Boston. (Plenaries are June 21-23 and exhibits are open June 21-22.) The Society for Vascular Surgery offers travel awards, including complimentary VAM registration, to be used toward the cost of travel, housing and meals.
Two awards are available, the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.
The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada.
Urge students you know with an interest in research to apply today.
DDSEP® 8 Quick Quiz - January 2018 Question 2
Q2. CORRECT ANSWER: C
RATIONALE
In a population study of U.S. veterans infected with hepatitis C (n = 110,484), a cox proportional hazards model was used to determine risk of developing cirrhosis and hepatocellular carcinoma for genotypes 1-4, after adjusting for age, period of service, race, sex, human immunodeficiency virus (HIV) infection, alcohol use, diabetes, body mass index, and antiviral treatment. Despite genotype 3 patients being younger, their risk of developing cirrhosis was highest with hazard ratio = 1.30 (1.22, 1.39), compared to genotype 1 (reference, HR 1.0), genotype 2 with HR = 0.68 (0.64, 0.73), and genotype 4 with HR = 0.94 (0.78, 1.14). Likewise, the risk of development of HCC was highest for genotype 3 HCV with HR = 1.80 (1.60, 2.03), compared to a genotype 2 (HR = 0.55; 0.47, 0.63), and genotype 4 (0.99; 0.68, 1.45).
It is speculated that the hepatic steatosis that is a direct result of genotype 3 HCV may contribute to the accelerated progression to cirrhosis and HCC, but this has not been proven and was not evaluated in this Veteran Affairs study.
REFERENCE
1. Kanwal F., Kramer J.R., Ilyas J., et al. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014;60(1):98-105.
Q2. CORRECT ANSWER: C
RATIONALE
In a population study of U.S. veterans infected with hepatitis C (n = 110,484), a cox proportional hazards model was used to determine risk of developing cirrhosis and hepatocellular carcinoma for genotypes 1-4, after adjusting for age, period of service, race, sex, human immunodeficiency virus (HIV) infection, alcohol use, diabetes, body mass index, and antiviral treatment. Despite genotype 3 patients being younger, their risk of developing cirrhosis was highest with hazard ratio = 1.30 (1.22, 1.39), compared to genotype 1 (reference, HR 1.0), genotype 2 with HR = 0.68 (0.64, 0.73), and genotype 4 with HR = 0.94 (0.78, 1.14). Likewise, the risk of development of HCC was highest for genotype 3 HCV with HR = 1.80 (1.60, 2.03), compared to a genotype 2 (HR = 0.55; 0.47, 0.63), and genotype 4 (0.99; 0.68, 1.45).
It is speculated that the hepatic steatosis that is a direct result of genotype 3 HCV may contribute to the accelerated progression to cirrhosis and HCC, but this has not been proven and was not evaluated in this Veteran Affairs study.
REFERENCE
1. Kanwal F., Kramer J.R., Ilyas J., et al. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014;60(1):98-105.
Q2. CORRECT ANSWER: C
RATIONALE
In a population study of U.S. veterans infected with hepatitis C (n = 110,484), a cox proportional hazards model was used to determine risk of developing cirrhosis and hepatocellular carcinoma for genotypes 1-4, after adjusting for age, period of service, race, sex, human immunodeficiency virus (HIV) infection, alcohol use, diabetes, body mass index, and antiviral treatment. Despite genotype 3 patients being younger, their risk of developing cirrhosis was highest with hazard ratio = 1.30 (1.22, 1.39), compared to genotype 1 (reference, HR 1.0), genotype 2 with HR = 0.68 (0.64, 0.73), and genotype 4 with HR = 0.94 (0.78, 1.14). Likewise, the risk of development of HCC was highest for genotype 3 HCV with HR = 1.80 (1.60, 2.03), compared to a genotype 2 (HR = 0.55; 0.47, 0.63), and genotype 4 (0.99; 0.68, 1.45).
It is speculated that the hepatic steatosis that is a direct result of genotype 3 HCV may contribute to the accelerated progression to cirrhosis and HCC, but this has not been proven and was not evaluated in this Veteran Affairs study.
REFERENCE
1. Kanwal F., Kramer J.R., Ilyas J., et al. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014;60(1):98-105.
Which HCV genotype is associated with the highest risk of cirrhosis and hepatocellular carcinoma?