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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?
MACRA Monday: Depression screening
If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.
Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.
Consider this measure:
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Measure #134: Preventive Care and Screening: Screening for Depression and Follow-Up Plan
This measure aims to capture the percentage of patients aged 12 years and older who have been screened for depression and have a documented follow-up plan of care, if appropriate.
What you need to do: Use an age-appropriate, standardized tool to screen patients for depression during the visit. If they screen positive, develop a follow-up plan during the visit and document it.
Eligible cases include patients who were aged 12 years or older on the date of the encounter and have a patient encounter during the performance period. Applicable codes include (CPT or HCPCS): 90791, 90792, 90832, 90834, 90837, 92625, 96116, 96118, 96150, 96151, 97165, 97166, 97167, 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215, G0101, G0402, G0438, G0439, G0444.
To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, G8431 indicates that depression screening was positive and a follow-up plan was documented, while G8510 indicates that the depression screening was negative and a follow-up plan is not required. Use exclusion code G9717 if the patient has an active diagnosis of depression for bipolar disorder.
CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.
Certain clinicians are exempt from reporting and do not face a penalty under MIPS:
- Those who enrolled in Medicare for the first time during a performance period.
- Those who have Medicare Part B allowed charges of $30,000 or less.
- Those who have 100 or fewer Medicare Part B patients.
- Those who are significantly participating in an Advanced Alternative Payment Model (APM).
If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.
Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.
Consider this measure:
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Measure #134: Preventive Care and Screening: Screening for Depression and Follow-Up Plan
This measure aims to capture the percentage of patients aged 12 years and older who have been screened for depression and have a documented follow-up plan of care, if appropriate.
What you need to do: Use an age-appropriate, standardized tool to screen patients for depression during the visit. If they screen positive, develop a follow-up plan during the visit and document it.
Eligible cases include patients who were aged 12 years or older on the date of the encounter and have a patient encounter during the performance period. Applicable codes include (CPT or HCPCS): 90791, 90792, 90832, 90834, 90837, 92625, 96116, 96118, 96150, 96151, 97165, 97166, 97167, 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215, G0101, G0402, G0438, G0439, G0444.
To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, G8431 indicates that depression screening was positive and a follow-up plan was documented, while G8510 indicates that the depression screening was negative and a follow-up plan is not required. Use exclusion code G9717 if the patient has an active diagnosis of depression for bipolar disorder.
CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.
Certain clinicians are exempt from reporting and do not face a penalty under MIPS:
- Those who enrolled in Medicare for the first time during a performance period.
- Those who have Medicare Part B allowed charges of $30,000 or less.
- Those who have 100 or fewer Medicare Part B patients.
- Those who are significantly participating in an Advanced Alternative Payment Model (APM).
If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.
Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.
Consider this measure:
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Measure #134: Preventive Care and Screening: Screening for Depression and Follow-Up Plan
This measure aims to capture the percentage of patients aged 12 years and older who have been screened for depression and have a documented follow-up plan of care, if appropriate.
What you need to do: Use an age-appropriate, standardized tool to screen patients for depression during the visit. If they screen positive, develop a follow-up plan during the visit and document it.
Eligible cases include patients who were aged 12 years or older on the date of the encounter and have a patient encounter during the performance period. Applicable codes include (CPT or HCPCS): 90791, 90792, 90832, 90834, 90837, 92625, 96116, 96118, 96150, 96151, 97165, 97166, 97167, 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215, G0101, G0402, G0438, G0439, G0444.
To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, G8431 indicates that depression screening was positive and a follow-up plan was documented, while G8510 indicates that the depression screening was negative and a follow-up plan is not required. Use exclusion code G9717 if the patient has an active diagnosis of depression for bipolar disorder.
CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.
Certain clinicians are exempt from reporting and do not face a penalty under MIPS:
- Those who enrolled in Medicare for the first time during a performance period.
- Those who have Medicare Part B allowed charges of $30,000 or less.
- Those who have 100 or fewer Medicare Part B patients.
- Those who are significantly participating in an Advanced Alternative Payment Model (APM).
Medication-Induced Pruritus From Direct Oral Anticoagulants
Pruritus is a subjective report of itching, which can be caused by dermatologic or systemic conditions. Pruritus accounts for about 5% of all skin adverse drug reactions (ADRs) after administration.1 Mechanisms by which medication-induced pruritus occurs are still unknown and have been understudied. Treatment modalities also have been understudied; however, the understood method for treatment is cessation of the causative agent.2
Anticoagulants commonly are used in several conditions, including prevention of ischemic cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) as well as for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE).3 Traditionally, warfarin was the gold standard anticoagulant. With the relatively recent approval of several direct oral anticoagulants (DOACs), such as rivaroxaban, apixaban, and dabigatran, the landscape of anticoagulation is changing. One benefit of using DOACs as opposed to warfarin is that they often require less frequent laboratory monitoring. However, rare ADRs not detected during clinical trials have appeared following drug approval.4
In a VA anticoagulation clinic that managed more than 60 patients taking DOACs, the authors identified 2 cases of pruritus, possibly associated with DOAC agents. These 2 cases point to a higher incidence rate than the rate reported in the rivaroxaban package insert (2%).5 Of note, pruritus is not mentioned in the apixaban package insert.6
Patient 1 Case Presentation
Patient 1 was a 69-year-old male with AF who was switched to rivaroxaban after 5 years of warfarin therapy. Past medical history included iron deficiency anemia, hypertension, type 2 diabetes mellitus, systolic heart failure, hyperlipidemia, hepatic steatosis, benign prostatic hyperplasia, and gastroesophageal reflux disease. The patient reported “itching all over” soon after initiation of rivaroxaban and that the itching was intolerable and always began 90 to 120 minutes after each dose of rivaroxaban with no associated rash.
After about 6 months of treatment with rivaroxaban, the patient was switched to apixaban; however, the pruritus persisted even after the switch. The onset of itching had similar timing with regard to the apixaban doses. When apixaban was initiated, the patient also was started on amiodarone and tamsulosin. A full pharmacotherapy review of the patient’s medication list for the incidence of pruritus was conducted. Regarding amiodarone and tamsulosin, incidence of pruritus was < 1%.7,8 Neither agent had yet been started during the rivaroxaban therapy; therefore, it was unlikely that either of these 2 medications were the causative agent of the pruritic ADR.
In response to the itching, the patient was given diphenhydramine 25 mg twice daily, taken with each dose of apixaban. Shortly thereafter, the patient reported that diphenhydramine lessened the severity of the pruritus. He was switched to loratadine 10 mg twice daily with each dose of apixaban, to avoid drowsiness as well as the increased anticholinergic ADRs of first-generation antihistamines. The patient reported that the itching was tolerable.
Patient 2 Case Presentation
Patient 2 was a 63-year-old male with AF and hypertension who was initially started on rivaroxaban and reported pruritus after about 1 month. Despite the uncomfortable itch, the patient elected to continue therapy and began diphenhydramine 25 mg daily with each dose of rivaroxaban. Diphenhydramine seemed to improve the pruritus but did not completely alleviate it. While on rivaroxaban, the patient experienced an acute drop in hemoglobin; however, no source of bleeding was found. Although the pruritus was largely resolved, he was switched to apixaban due to its favorable bleeding profile.9 The patient continued to have pruritus on apixaban; however, he reported that pruritus was less severe than it had been while taking rivaroxaban. The patient restarted on diphenhydramine twice daily with each dose of apixaban and reported cessation of pruritus.
Discussion
After observing both cases in relation to the timing between the administration of a DOAC and onset of pruritus, it seemed likely that the causative agent could be the DOAC. A Naranjo Nomogram was used to determine the likeliness of each drug to be the causative agent of the ADR.10 This nomogram is scaled from a low score of -4 to a high score of 13. Patients 1 and 2 had a score of 4, which is reflective of a possible ADR (score 1-4). Using the nomogram as well as the subjective information provided by the patients, it is reasonable to conclude that the pruritus was possibly associated with the use of the DOACs. Nonadherence to anticoagulants may lead to potentially fatal adverse outcomes, such as stroke. Medication-associated pruritus could lead to medication nonadherence if left unaddressed. It is notable that prescribing an antihistamine that is taken at the time of the anticoagulant dose allowed these patients with possible DOAC-associated pruritus to continue therapy with the selected anticoagulant. Further research on this topic is needed.
1. Reich A, Ständer S, Szepietowski C. Drug-induced pruritus: a review. Acta Derm Venereol. 2009;89(3):236-244.
2. Ebata T. Drug-induced itch management. Curr Probl Dermatol. 2016;50:155-163.
3. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-232.
4. U.S. Department of Health and Human Services, U.S. Food & Drug Administration. FDA Adverse Events Reporting System (FAERS) public dashboard. Apixaban. https://fis.fda.gov/sense/app/777e9f4d-0cf8-448e-8068-f564c31baa25/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis. Updated August 31, 2017. Accessed November 8, 2017.
5. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2011.
6. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; New York, NY: Pfizer Inc; 2016.
7. Pacerone [package insert]. Minneapolis, MN: Upsher-Smith Laboratories Inc; 2008. Minneapolis, MN.
8. Flomax [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2016.
9. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patient with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
10. Michel DJ, Knodel LC. Comparison of three algorithms used to evaluate adverse drug reactions. Am J Hosp Pharm. 1986;43(7):1709-1714.
Pruritus is a subjective report of itching, which can be caused by dermatologic or systemic conditions. Pruritus accounts for about 5% of all skin adverse drug reactions (ADRs) after administration.1 Mechanisms by which medication-induced pruritus occurs are still unknown and have been understudied. Treatment modalities also have been understudied; however, the understood method for treatment is cessation of the causative agent.2
Anticoagulants commonly are used in several conditions, including prevention of ischemic cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) as well as for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE).3 Traditionally, warfarin was the gold standard anticoagulant. With the relatively recent approval of several direct oral anticoagulants (DOACs), such as rivaroxaban, apixaban, and dabigatran, the landscape of anticoagulation is changing. One benefit of using DOACs as opposed to warfarin is that they often require less frequent laboratory monitoring. However, rare ADRs not detected during clinical trials have appeared following drug approval.4
In a VA anticoagulation clinic that managed more than 60 patients taking DOACs, the authors identified 2 cases of pruritus, possibly associated with DOAC agents. These 2 cases point to a higher incidence rate than the rate reported in the rivaroxaban package insert (2%).5 Of note, pruritus is not mentioned in the apixaban package insert.6
Patient 1 Case Presentation
Patient 1 was a 69-year-old male with AF who was switched to rivaroxaban after 5 years of warfarin therapy. Past medical history included iron deficiency anemia, hypertension, type 2 diabetes mellitus, systolic heart failure, hyperlipidemia, hepatic steatosis, benign prostatic hyperplasia, and gastroesophageal reflux disease. The patient reported “itching all over” soon after initiation of rivaroxaban and that the itching was intolerable and always began 90 to 120 minutes after each dose of rivaroxaban with no associated rash.
After about 6 months of treatment with rivaroxaban, the patient was switched to apixaban; however, the pruritus persisted even after the switch. The onset of itching had similar timing with regard to the apixaban doses. When apixaban was initiated, the patient also was started on amiodarone and tamsulosin. A full pharmacotherapy review of the patient’s medication list for the incidence of pruritus was conducted. Regarding amiodarone and tamsulosin, incidence of pruritus was < 1%.7,8 Neither agent had yet been started during the rivaroxaban therapy; therefore, it was unlikely that either of these 2 medications were the causative agent of the pruritic ADR.
In response to the itching, the patient was given diphenhydramine 25 mg twice daily, taken with each dose of apixaban. Shortly thereafter, the patient reported that diphenhydramine lessened the severity of the pruritus. He was switched to loratadine 10 mg twice daily with each dose of apixaban, to avoid drowsiness as well as the increased anticholinergic ADRs of first-generation antihistamines. The patient reported that the itching was tolerable.
Patient 2 Case Presentation
Patient 2 was a 63-year-old male with AF and hypertension who was initially started on rivaroxaban and reported pruritus after about 1 month. Despite the uncomfortable itch, the patient elected to continue therapy and began diphenhydramine 25 mg daily with each dose of rivaroxaban. Diphenhydramine seemed to improve the pruritus but did not completely alleviate it. While on rivaroxaban, the patient experienced an acute drop in hemoglobin; however, no source of bleeding was found. Although the pruritus was largely resolved, he was switched to apixaban due to its favorable bleeding profile.9 The patient continued to have pruritus on apixaban; however, he reported that pruritus was less severe than it had been while taking rivaroxaban. The patient restarted on diphenhydramine twice daily with each dose of apixaban and reported cessation of pruritus.
Discussion
After observing both cases in relation to the timing between the administration of a DOAC and onset of pruritus, it seemed likely that the causative agent could be the DOAC. A Naranjo Nomogram was used to determine the likeliness of each drug to be the causative agent of the ADR.10 This nomogram is scaled from a low score of -4 to a high score of 13. Patients 1 and 2 had a score of 4, which is reflective of a possible ADR (score 1-4). Using the nomogram as well as the subjective information provided by the patients, it is reasonable to conclude that the pruritus was possibly associated with the use of the DOACs. Nonadherence to anticoagulants may lead to potentially fatal adverse outcomes, such as stroke. Medication-associated pruritus could lead to medication nonadherence if left unaddressed. It is notable that prescribing an antihistamine that is taken at the time of the anticoagulant dose allowed these patients with possible DOAC-associated pruritus to continue therapy with the selected anticoagulant. Further research on this topic is needed.
Pruritus is a subjective report of itching, which can be caused by dermatologic or systemic conditions. Pruritus accounts for about 5% of all skin adverse drug reactions (ADRs) after administration.1 Mechanisms by which medication-induced pruritus occurs are still unknown and have been understudied. Treatment modalities also have been understudied; however, the understood method for treatment is cessation of the causative agent.2
Anticoagulants commonly are used in several conditions, including prevention of ischemic cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) as well as for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE).3 Traditionally, warfarin was the gold standard anticoagulant. With the relatively recent approval of several direct oral anticoagulants (DOACs), such as rivaroxaban, apixaban, and dabigatran, the landscape of anticoagulation is changing. One benefit of using DOACs as opposed to warfarin is that they often require less frequent laboratory monitoring. However, rare ADRs not detected during clinical trials have appeared following drug approval.4
In a VA anticoagulation clinic that managed more than 60 patients taking DOACs, the authors identified 2 cases of pruritus, possibly associated with DOAC agents. These 2 cases point to a higher incidence rate than the rate reported in the rivaroxaban package insert (2%).5 Of note, pruritus is not mentioned in the apixaban package insert.6
Patient 1 Case Presentation
Patient 1 was a 69-year-old male with AF who was switched to rivaroxaban after 5 years of warfarin therapy. Past medical history included iron deficiency anemia, hypertension, type 2 diabetes mellitus, systolic heart failure, hyperlipidemia, hepatic steatosis, benign prostatic hyperplasia, and gastroesophageal reflux disease. The patient reported “itching all over” soon after initiation of rivaroxaban and that the itching was intolerable and always began 90 to 120 minutes after each dose of rivaroxaban with no associated rash.
After about 6 months of treatment with rivaroxaban, the patient was switched to apixaban; however, the pruritus persisted even after the switch. The onset of itching had similar timing with regard to the apixaban doses. When apixaban was initiated, the patient also was started on amiodarone and tamsulosin. A full pharmacotherapy review of the patient’s medication list for the incidence of pruritus was conducted. Regarding amiodarone and tamsulosin, incidence of pruritus was < 1%.7,8 Neither agent had yet been started during the rivaroxaban therapy; therefore, it was unlikely that either of these 2 medications were the causative agent of the pruritic ADR.
In response to the itching, the patient was given diphenhydramine 25 mg twice daily, taken with each dose of apixaban. Shortly thereafter, the patient reported that diphenhydramine lessened the severity of the pruritus. He was switched to loratadine 10 mg twice daily with each dose of apixaban, to avoid drowsiness as well as the increased anticholinergic ADRs of first-generation antihistamines. The patient reported that the itching was tolerable.
Patient 2 Case Presentation
Patient 2 was a 63-year-old male with AF and hypertension who was initially started on rivaroxaban and reported pruritus after about 1 month. Despite the uncomfortable itch, the patient elected to continue therapy and began diphenhydramine 25 mg daily with each dose of rivaroxaban. Diphenhydramine seemed to improve the pruritus but did not completely alleviate it. While on rivaroxaban, the patient experienced an acute drop in hemoglobin; however, no source of bleeding was found. Although the pruritus was largely resolved, he was switched to apixaban due to its favorable bleeding profile.9 The patient continued to have pruritus on apixaban; however, he reported that pruritus was less severe than it had been while taking rivaroxaban. The patient restarted on diphenhydramine twice daily with each dose of apixaban and reported cessation of pruritus.
Discussion
After observing both cases in relation to the timing between the administration of a DOAC and onset of pruritus, it seemed likely that the causative agent could be the DOAC. A Naranjo Nomogram was used to determine the likeliness of each drug to be the causative agent of the ADR.10 This nomogram is scaled from a low score of -4 to a high score of 13. Patients 1 and 2 had a score of 4, which is reflective of a possible ADR (score 1-4). Using the nomogram as well as the subjective information provided by the patients, it is reasonable to conclude that the pruritus was possibly associated with the use of the DOACs. Nonadherence to anticoagulants may lead to potentially fatal adverse outcomes, such as stroke. Medication-associated pruritus could lead to medication nonadherence if left unaddressed. It is notable that prescribing an antihistamine that is taken at the time of the anticoagulant dose allowed these patients with possible DOAC-associated pruritus to continue therapy with the selected anticoagulant. Further research on this topic is needed.
1. Reich A, Ständer S, Szepietowski C. Drug-induced pruritus: a review. Acta Derm Venereol. 2009;89(3):236-244.
2. Ebata T. Drug-induced itch management. Curr Probl Dermatol. 2016;50:155-163.
3. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-232.
4. U.S. Department of Health and Human Services, U.S. Food & Drug Administration. FDA Adverse Events Reporting System (FAERS) public dashboard. Apixaban. https://fis.fda.gov/sense/app/777e9f4d-0cf8-448e-8068-f564c31baa25/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis. Updated August 31, 2017. Accessed November 8, 2017.
5. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2011.
6. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; New York, NY: Pfizer Inc; 2016.
7. Pacerone [package insert]. Minneapolis, MN: Upsher-Smith Laboratories Inc; 2008. Minneapolis, MN.
8. Flomax [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2016.
9. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patient with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
10. Michel DJ, Knodel LC. Comparison of three algorithms used to evaluate adverse drug reactions. Am J Hosp Pharm. 1986;43(7):1709-1714.
1. Reich A, Ständer S, Szepietowski C. Drug-induced pruritus: a review. Acta Derm Venereol. 2009;89(3):236-244.
2. Ebata T. Drug-induced itch management. Curr Probl Dermatol. 2016;50:155-163.
3. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-232.
4. U.S. Department of Health and Human Services, U.S. Food & Drug Administration. FDA Adverse Events Reporting System (FAERS) public dashboard. Apixaban. https://fis.fda.gov/sense/app/777e9f4d-0cf8-448e-8068-f564c31baa25/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis. Updated August 31, 2017. Accessed November 8, 2017.
5. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2011.
6. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; New York, NY: Pfizer Inc; 2016.
7. Pacerone [package insert]. Minneapolis, MN: Upsher-Smith Laboratories Inc; 2008. Minneapolis, MN.
8. Flomax [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2016.
9. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patient with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
10. Michel DJ, Knodel LC. Comparison of three algorithms used to evaluate adverse drug reactions. Am J Hosp Pharm. 1986;43(7):1709-1714.