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Has the time come to bury BMI in favor of other screening measures?
In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.
For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:
- Underweight: BMI < 18.5
- Normal weight: BMI ≥ 18.5 to 24.9
- Overweight: BMI ≥ 25 to 29.9
- Obesity: BMI ≥ 30
Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.
BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m2 correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
BMI limitations
There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.
Body composition and adipose tissue
Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.
A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.
Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.
As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.
Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.
One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
Biomarkers
Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.
Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.
While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.
Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.
Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.
Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.
For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:
- Underweight: BMI < 18.5
- Normal weight: BMI ≥ 18.5 to 24.9
- Overweight: BMI ≥ 25 to 29.9
- Obesity: BMI ≥ 30
Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.
BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m2 correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
BMI limitations
There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.
Body composition and adipose tissue
Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.
A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.
Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.
As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.
Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.
One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
Biomarkers
Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.
Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.
While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.
Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.
Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.
Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.
For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:
- Underweight: BMI < 18.5
- Normal weight: BMI ≥ 18.5 to 24.9
- Overweight: BMI ≥ 25 to 29.9
- Obesity: BMI ≥ 30
Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.
BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m2 correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
BMI limitations
There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.
Body composition and adipose tissue
Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.
A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.
Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.
As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.
Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.
One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
Biomarkers
Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.
Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.
While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.
Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.
Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.
Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
One type of bariatric surgery betters IBD outcomes
Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.
Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.
“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.
The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
Outcomes compared with and without surgery
The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.
And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.
To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.
The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.
Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.
Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.
As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”
The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
Study helps confirm benefits of weight loss
Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.
“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.
“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.
Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.
“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.
Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.
Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.
“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.
The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
Outcomes compared with and without surgery
The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.
And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.
To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.
The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.
Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.
Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.
As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”
The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
Study helps confirm benefits of weight loss
Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.
“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.
“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.
Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.
“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.
Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.
Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.
“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.
The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
Outcomes compared with and without surgery
The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.
And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.
To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.
The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.
Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.
Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.
As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”
The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
Study helps confirm benefits of weight loss
Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.
“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.
“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.
Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.
“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.
Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
FROM JOURNAL OF CLINICAL GASTROENTEROLOGY
Debate: Initial combination therapy for type 2 diabetes?
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Study finds big growth in advanced-practice clinicians in Medicare dermatology
A .
Researchers from the University of Texas MD Anderson Cancer Center, Houston, and the University of Pennsylvania, Philadelphia, reported in JAMA Dermatology that in 2013 APCs made up 28% of the dermatology clinician workforce. By 2020, they made up 37% of the dermatology clinicians giving care to Medicare beneficiaries.
Retrospective cohort study
APCs provided care in 15.5% of dermatology office visits in 2013 and 27.4% in 2020 (P =.02), the authors reported. “By 2020, more than one in four dermatology visits for patients with Medicare were delivered by APCs,” wrote the authors, led by Mackenzie R. Wehner, MD, MPhil, assistant professor of dermatology and health services research at MD Anderson.
“Everyone in dermatology is aware of the increasing adoption of advanced practice clinicians in the field,” Justin D. Arnold, MD, MMSc, a 3rd-year dermatology resident at the University of California, Irvine, said in an interview. “However, seeing how quickly this happening and the absolute number of these clinicians is still startling,” said Dr. Arnold, who in 2022 published a research letter in JAMA Dermatology on the impact of physician assistants in dermatology.
In that study, he and his coauthors reported that the PA workforce in dermatology was growing faster than in other specialties.
In the current study, Dr. Wehner and her colleagues identified 8,444 dermatology APCs and 14,402 physician dermatologists who provided 109.3 million Medicare office visits from 2013 to 2020. More than 80% of the procedures were performed by physicians, but APCs appeared to increasingly be taking on more of the procedural load.
Over the study period, APCs had an average annual increase of 12.6% in the number of premalignant lesion destructions performed; physicians saw an average 1.4% decline. For skin biopsies, APCs performed 11.7% more per year on average, compared with a 1.4% drop for physicians.
“This data is not surprising given most agree that skin biopsies and destruction of premalignant lesions are well within the scope of practice of APCs,” Dr. Arnold told this news organization.
The authors also reported that, while most APCs – similar to physician dermatologists – practice in metropolitan areas, they are working in other locations also. Slightly more than half of dermatology clinicians in micropolitan areas are APCs, and in rural areas, 88% of clinicians are APCs, Dr. Wehner and colleagues found.
APCs may be filling a gap in rural areas for Medicare patients, said Dr. Arnold, but, he added, “it is unclear if dermatology APCs are growing as quickly in practices that predominantly accept Medicaid and if dermatology APCs are expanding access to these populations.”
Dr. Arnold said he expected the number of APCs in dermatology to continue growing, serving commercially insured patients, as well. “There are a multitude of potential reasons for more APCs in dermatology, including difficulty recruiting dermatologists in rural communities, financial motivators, and the expansion of private equity, and the increasing acceptance of these clinicians within medicine and by patients.”
APCs can provide good-quality care if they are properly trained and supervised, said Dr. Arnold, adding that he is concerned, however, that the training and supervision is not being provided. “This study provides further evidence that dermatologists, and national dermatology organizations such as the AAD [American Academy of Dermatology], need to take a more active role in the leadership of APC training,” he said.
Dermatology, he noted, “would benefit from consensus guidelines on clinical competencies for dermatology APCs,” similar to an effort by the American College of Cardiology.
A review* published online in July noted that, compared with dermatologists, some data suggest that non-physician operators (NPOs) may have a higher rate of adverse events when performing aesthetic procedures, according to the authors of the review, led by Shelby L. Kubicki, MD, of the department of dermatology at the UTHealth Science Center in Houston. There is no mandatory reporting of complications for nonphysician providers, so the authors relied on data from cosmetic-focused practices, medical spas, and a survey by the American Society of Dermatologic Surgery of consumers and its members. More than half of the responding physicians “reported treating complications of a cosmetic procedure performed by an NPO,” the authors wrote.
They also found higher rates of burns and discoloration among patients who were treated by NPOs. The injuries occurred primarily at medical spas.
“Although NPOs may help to meet the rising demand for dermatologic procedures, care should still be taken to prioritize patient safety and outcomes above all else, including financial profits and revenues,” the authors wrote.
Dr. Wehner and her colleagues report no relevant financial relationships. Their study research was supported, in part, by a Cancer Center Support Grant and by the Cancer Prevention and Research Institute of Texas. Dr. Arnold also reports no relevant financial relationships. No author disclosures or funding information were available for the Clinics in Dermatology paper.
*Correction, 12/8/23: An earlier version of this story misstated the study design.
A .
Researchers from the University of Texas MD Anderson Cancer Center, Houston, and the University of Pennsylvania, Philadelphia, reported in JAMA Dermatology that in 2013 APCs made up 28% of the dermatology clinician workforce. By 2020, they made up 37% of the dermatology clinicians giving care to Medicare beneficiaries.
Retrospective cohort study
APCs provided care in 15.5% of dermatology office visits in 2013 and 27.4% in 2020 (P =.02), the authors reported. “By 2020, more than one in four dermatology visits for patients with Medicare were delivered by APCs,” wrote the authors, led by Mackenzie R. Wehner, MD, MPhil, assistant professor of dermatology and health services research at MD Anderson.
“Everyone in dermatology is aware of the increasing adoption of advanced practice clinicians in the field,” Justin D. Arnold, MD, MMSc, a 3rd-year dermatology resident at the University of California, Irvine, said in an interview. “However, seeing how quickly this happening and the absolute number of these clinicians is still startling,” said Dr. Arnold, who in 2022 published a research letter in JAMA Dermatology on the impact of physician assistants in dermatology.
In that study, he and his coauthors reported that the PA workforce in dermatology was growing faster than in other specialties.
In the current study, Dr. Wehner and her colleagues identified 8,444 dermatology APCs and 14,402 physician dermatologists who provided 109.3 million Medicare office visits from 2013 to 2020. More than 80% of the procedures were performed by physicians, but APCs appeared to increasingly be taking on more of the procedural load.
Over the study period, APCs had an average annual increase of 12.6% in the number of premalignant lesion destructions performed; physicians saw an average 1.4% decline. For skin biopsies, APCs performed 11.7% more per year on average, compared with a 1.4% drop for physicians.
“This data is not surprising given most agree that skin biopsies and destruction of premalignant lesions are well within the scope of practice of APCs,” Dr. Arnold told this news organization.
The authors also reported that, while most APCs – similar to physician dermatologists – practice in metropolitan areas, they are working in other locations also. Slightly more than half of dermatology clinicians in micropolitan areas are APCs, and in rural areas, 88% of clinicians are APCs, Dr. Wehner and colleagues found.
APCs may be filling a gap in rural areas for Medicare patients, said Dr. Arnold, but, he added, “it is unclear if dermatology APCs are growing as quickly in practices that predominantly accept Medicaid and if dermatology APCs are expanding access to these populations.”
Dr. Arnold said he expected the number of APCs in dermatology to continue growing, serving commercially insured patients, as well. “There are a multitude of potential reasons for more APCs in dermatology, including difficulty recruiting dermatologists in rural communities, financial motivators, and the expansion of private equity, and the increasing acceptance of these clinicians within medicine and by patients.”
APCs can provide good-quality care if they are properly trained and supervised, said Dr. Arnold, adding that he is concerned, however, that the training and supervision is not being provided. “This study provides further evidence that dermatologists, and national dermatology organizations such as the AAD [American Academy of Dermatology], need to take a more active role in the leadership of APC training,” he said.
Dermatology, he noted, “would benefit from consensus guidelines on clinical competencies for dermatology APCs,” similar to an effort by the American College of Cardiology.
A review* published online in July noted that, compared with dermatologists, some data suggest that non-physician operators (NPOs) may have a higher rate of adverse events when performing aesthetic procedures, according to the authors of the review, led by Shelby L. Kubicki, MD, of the department of dermatology at the UTHealth Science Center in Houston. There is no mandatory reporting of complications for nonphysician providers, so the authors relied on data from cosmetic-focused practices, medical spas, and a survey by the American Society of Dermatologic Surgery of consumers and its members. More than half of the responding physicians “reported treating complications of a cosmetic procedure performed by an NPO,” the authors wrote.
They also found higher rates of burns and discoloration among patients who were treated by NPOs. The injuries occurred primarily at medical spas.
“Although NPOs may help to meet the rising demand for dermatologic procedures, care should still be taken to prioritize patient safety and outcomes above all else, including financial profits and revenues,” the authors wrote.
Dr. Wehner and her colleagues report no relevant financial relationships. Their study research was supported, in part, by a Cancer Center Support Grant and by the Cancer Prevention and Research Institute of Texas. Dr. Arnold also reports no relevant financial relationships. No author disclosures or funding information were available for the Clinics in Dermatology paper.
*Correction, 12/8/23: An earlier version of this story misstated the study design.
A .
Researchers from the University of Texas MD Anderson Cancer Center, Houston, and the University of Pennsylvania, Philadelphia, reported in JAMA Dermatology that in 2013 APCs made up 28% of the dermatology clinician workforce. By 2020, they made up 37% of the dermatology clinicians giving care to Medicare beneficiaries.
Retrospective cohort study
APCs provided care in 15.5% of dermatology office visits in 2013 and 27.4% in 2020 (P =.02), the authors reported. “By 2020, more than one in four dermatology visits for patients with Medicare were delivered by APCs,” wrote the authors, led by Mackenzie R. Wehner, MD, MPhil, assistant professor of dermatology and health services research at MD Anderson.
“Everyone in dermatology is aware of the increasing adoption of advanced practice clinicians in the field,” Justin D. Arnold, MD, MMSc, a 3rd-year dermatology resident at the University of California, Irvine, said in an interview. “However, seeing how quickly this happening and the absolute number of these clinicians is still startling,” said Dr. Arnold, who in 2022 published a research letter in JAMA Dermatology on the impact of physician assistants in dermatology.
In that study, he and his coauthors reported that the PA workforce in dermatology was growing faster than in other specialties.
In the current study, Dr. Wehner and her colleagues identified 8,444 dermatology APCs and 14,402 physician dermatologists who provided 109.3 million Medicare office visits from 2013 to 2020. More than 80% of the procedures were performed by physicians, but APCs appeared to increasingly be taking on more of the procedural load.
Over the study period, APCs had an average annual increase of 12.6% in the number of premalignant lesion destructions performed; physicians saw an average 1.4% decline. For skin biopsies, APCs performed 11.7% more per year on average, compared with a 1.4% drop for physicians.
“This data is not surprising given most agree that skin biopsies and destruction of premalignant lesions are well within the scope of practice of APCs,” Dr. Arnold told this news organization.
The authors also reported that, while most APCs – similar to physician dermatologists – practice in metropolitan areas, they are working in other locations also. Slightly more than half of dermatology clinicians in micropolitan areas are APCs, and in rural areas, 88% of clinicians are APCs, Dr. Wehner and colleagues found.
APCs may be filling a gap in rural areas for Medicare patients, said Dr. Arnold, but, he added, “it is unclear if dermatology APCs are growing as quickly in practices that predominantly accept Medicaid and if dermatology APCs are expanding access to these populations.”
Dr. Arnold said he expected the number of APCs in dermatology to continue growing, serving commercially insured patients, as well. “There are a multitude of potential reasons for more APCs in dermatology, including difficulty recruiting dermatologists in rural communities, financial motivators, and the expansion of private equity, and the increasing acceptance of these clinicians within medicine and by patients.”
APCs can provide good-quality care if they are properly trained and supervised, said Dr. Arnold, adding that he is concerned, however, that the training and supervision is not being provided. “This study provides further evidence that dermatologists, and national dermatology organizations such as the AAD [American Academy of Dermatology], need to take a more active role in the leadership of APC training,” he said.
Dermatology, he noted, “would benefit from consensus guidelines on clinical competencies for dermatology APCs,” similar to an effort by the American College of Cardiology.
A review* published online in July noted that, compared with dermatologists, some data suggest that non-physician operators (NPOs) may have a higher rate of adverse events when performing aesthetic procedures, according to the authors of the review, led by Shelby L. Kubicki, MD, of the department of dermatology at the UTHealth Science Center in Houston. There is no mandatory reporting of complications for nonphysician providers, so the authors relied on data from cosmetic-focused practices, medical spas, and a survey by the American Society of Dermatologic Surgery of consumers and its members. More than half of the responding physicians “reported treating complications of a cosmetic procedure performed by an NPO,” the authors wrote.
They also found higher rates of burns and discoloration among patients who were treated by NPOs. The injuries occurred primarily at medical spas.
“Although NPOs may help to meet the rising demand for dermatologic procedures, care should still be taken to prioritize patient safety and outcomes above all else, including financial profits and revenues,” the authors wrote.
Dr. Wehner and her colleagues report no relevant financial relationships. Their study research was supported, in part, by a Cancer Center Support Grant and by the Cancer Prevention and Research Institute of Texas. Dr. Arnold also reports no relevant financial relationships. No author disclosures or funding information were available for the Clinics in Dermatology paper.
*Correction, 12/8/23: An earlier version of this story misstated the study design.
FROM JAMA DERMATOLOGY
Expanded coverage of carotid stenting in CMS draft proposal
The new memo follows a national coverage analysis for CAS that was initiated in January 2023 and considers 193 public comments received in the ensuing month.
That analysis followed a request from the Multispecialty Carotid Alliance (MSCA) to make the existing guidelines less restrictive.
The decision proposal would expand coverage for CAS “to standard surgical risk patients by removing the limitation of coverage to only high surgical risk patients.” It would limit it to patients for whom CAS is considered “reasonable and necessary” and who are either symptomatic with carotid stenosis of 50% or greater or asymptomatic with carotid stenosis of at least 70%.
The proposal would require practitioners to “engage in a formal shared decision-making interaction with the beneficiary” that involves use of a “validated decision-making tool.” The conversation must include discussion of all treatment options and their risks and benefits and cover information from the clinical guidelines, as well as “incorporate the patient’s personal preferences and priorities.”
Much of the proposed coverage criteria resemble recommendations from several societies that offered comments in response to the Jan. 12 CMS statement that led to the current draft proposal. They include, along with MSCA, the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, and jointly the American College of Cardiology and the American Heart Association.
Carotid stenting, commented the ACC/AHA, “was first introduced in 1994, and the field has matured in the last 3 decades.” The procedure “is a well-established treatment option.” The groups declared support for “removal of the facility and operator requirement for CAS consistent with the current state of the published literature and standard clinical practice.”
The current CMS draft proposal acknowledges the publication of five major randomized controlled trials and a number of “large, prospective registry-based studies” since 2009 that support its proposed coverage criteria.
Collectively, it states, the evidence “suffices to demonstrate that CAS and [carotid endarterectomy] are similarly effective” with respect to the clinical primary endpoints of recent trials “in patients with either standard or high surgical risk and who are symptomatic with carotid artery stenosis ≥ 50% or asymptomatic with stenosis ≥ 70%.”
A version of this article appeared on Medscape.com.
The new memo follows a national coverage analysis for CAS that was initiated in January 2023 and considers 193 public comments received in the ensuing month.
That analysis followed a request from the Multispecialty Carotid Alliance (MSCA) to make the existing guidelines less restrictive.
The decision proposal would expand coverage for CAS “to standard surgical risk patients by removing the limitation of coverage to only high surgical risk patients.” It would limit it to patients for whom CAS is considered “reasonable and necessary” and who are either symptomatic with carotid stenosis of 50% or greater or asymptomatic with carotid stenosis of at least 70%.
The proposal would require practitioners to “engage in a formal shared decision-making interaction with the beneficiary” that involves use of a “validated decision-making tool.” The conversation must include discussion of all treatment options and their risks and benefits and cover information from the clinical guidelines, as well as “incorporate the patient’s personal preferences and priorities.”
Much of the proposed coverage criteria resemble recommendations from several societies that offered comments in response to the Jan. 12 CMS statement that led to the current draft proposal. They include, along with MSCA, the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, and jointly the American College of Cardiology and the American Heart Association.
Carotid stenting, commented the ACC/AHA, “was first introduced in 1994, and the field has matured in the last 3 decades.” The procedure “is a well-established treatment option.” The groups declared support for “removal of the facility and operator requirement for CAS consistent with the current state of the published literature and standard clinical practice.”
The current CMS draft proposal acknowledges the publication of five major randomized controlled trials and a number of “large, prospective registry-based studies” since 2009 that support its proposed coverage criteria.
Collectively, it states, the evidence “suffices to demonstrate that CAS and [carotid endarterectomy] are similarly effective” with respect to the clinical primary endpoints of recent trials “in patients with either standard or high surgical risk and who are symptomatic with carotid artery stenosis ≥ 50% or asymptomatic with stenosis ≥ 70%.”
A version of this article appeared on Medscape.com.
The new memo follows a national coverage analysis for CAS that was initiated in January 2023 and considers 193 public comments received in the ensuing month.
That analysis followed a request from the Multispecialty Carotid Alliance (MSCA) to make the existing guidelines less restrictive.
The decision proposal would expand coverage for CAS “to standard surgical risk patients by removing the limitation of coverage to only high surgical risk patients.” It would limit it to patients for whom CAS is considered “reasonable and necessary” and who are either symptomatic with carotid stenosis of 50% or greater or asymptomatic with carotid stenosis of at least 70%.
The proposal would require practitioners to “engage in a formal shared decision-making interaction with the beneficiary” that involves use of a “validated decision-making tool.” The conversation must include discussion of all treatment options and their risks and benefits and cover information from the clinical guidelines, as well as “incorporate the patient’s personal preferences and priorities.”
Much of the proposed coverage criteria resemble recommendations from several societies that offered comments in response to the Jan. 12 CMS statement that led to the current draft proposal. They include, along with MSCA, the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, and jointly the American College of Cardiology and the American Heart Association.
Carotid stenting, commented the ACC/AHA, “was first introduced in 1994, and the field has matured in the last 3 decades.” The procedure “is a well-established treatment option.” The groups declared support for “removal of the facility and operator requirement for CAS consistent with the current state of the published literature and standard clinical practice.”
The current CMS draft proposal acknowledges the publication of five major randomized controlled trials and a number of “large, prospective registry-based studies” since 2009 that support its proposed coverage criteria.
Collectively, it states, the evidence “suffices to demonstrate that CAS and [carotid endarterectomy] are similarly effective” with respect to the clinical primary endpoints of recent trials “in patients with either standard or high surgical risk and who are symptomatic with carotid artery stenosis ≥ 50% or asymptomatic with stenosis ≥ 70%.”
A version of this article appeared on Medscape.com.
LAMA-LABA surpasses corticosteroid combination as COPD therapy
Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.
Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.
Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.
The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.
The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.
Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
Findings clarify clinical practice guidelines
“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.
“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.
However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.
“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.
The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.
Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.
Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.
Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.
Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.
The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.
The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.
Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
Findings clarify clinical practice guidelines
“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.
“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.
However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.
“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.
The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.
Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.
Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.
Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.
Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.
The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.
The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.
Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
Findings clarify clinical practice guidelines
“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.
“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.
However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.
“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.
The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.
Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.
FROM JAMA INTERNAL MEDICINE
Fibromyalgia linked to higher mortality risk
People who experience chronic pain and tiredness from fibromyalgia have an increased risk for all-cause mortality, a new analysis of evidence says.
The condition can lead people to be vulnerable to accidents, infections, and even suicide, according to the report published in RMD Open.
The researchers suggest that care providers monitor physical and mental health to lower the dangers.
People with fibromyalgia often have other health issues, including rheumatic, gut, neurological, and mental health disorders, according to The BMJ. More and more people are being diagnosed with fibromyalgia. The cause of the illness remains unclear.
The researchers looked at eight studies published between 1999 and 2020 and pooled results from six of them. The studies involved a total of 188,000 adults.
The analysis of the data revealed that fibromyalgia was linked to a 27% greater risk of death from all causes.
Those with fibromyalgia were at a 44% greater risk of infections, including pneumonia. Their suicide risk was more than three times higher.
The greater risk of all-cause death could result from fatigue, poor sleep, and concentration problems, The BMJ said.
The patients had a 12% lower risk of dying from cancer, the analysis found. This could be because they tend to make more visits to health care professionals, the authors suggest.
“Fibromyalgia is often called an ‘imaginary condition,’ with ongoing debates on the legitimacy and clinical usefulness of this diagnosis. Our review provides further proof that fibromyalgia patients should be taken seriously, with particular focus on screening for suicidal ideation, prevention of accidents, and prevention and treatment of infections,” the researchers say.
A version of this article appeared on WebMD.com.
People who experience chronic pain and tiredness from fibromyalgia have an increased risk for all-cause mortality, a new analysis of evidence says.
The condition can lead people to be vulnerable to accidents, infections, and even suicide, according to the report published in RMD Open.
The researchers suggest that care providers monitor physical and mental health to lower the dangers.
People with fibromyalgia often have other health issues, including rheumatic, gut, neurological, and mental health disorders, according to The BMJ. More and more people are being diagnosed with fibromyalgia. The cause of the illness remains unclear.
The researchers looked at eight studies published between 1999 and 2020 and pooled results from six of them. The studies involved a total of 188,000 adults.
The analysis of the data revealed that fibromyalgia was linked to a 27% greater risk of death from all causes.
Those with fibromyalgia were at a 44% greater risk of infections, including pneumonia. Their suicide risk was more than three times higher.
The greater risk of all-cause death could result from fatigue, poor sleep, and concentration problems, The BMJ said.
The patients had a 12% lower risk of dying from cancer, the analysis found. This could be because they tend to make more visits to health care professionals, the authors suggest.
“Fibromyalgia is often called an ‘imaginary condition,’ with ongoing debates on the legitimacy and clinical usefulness of this diagnosis. Our review provides further proof that fibromyalgia patients should be taken seriously, with particular focus on screening for suicidal ideation, prevention of accidents, and prevention and treatment of infections,” the researchers say.
A version of this article appeared on WebMD.com.
People who experience chronic pain and tiredness from fibromyalgia have an increased risk for all-cause mortality, a new analysis of evidence says.
The condition can lead people to be vulnerable to accidents, infections, and even suicide, according to the report published in RMD Open.
The researchers suggest that care providers monitor physical and mental health to lower the dangers.
People with fibromyalgia often have other health issues, including rheumatic, gut, neurological, and mental health disorders, according to The BMJ. More and more people are being diagnosed with fibromyalgia. The cause of the illness remains unclear.
The researchers looked at eight studies published between 1999 and 2020 and pooled results from six of them. The studies involved a total of 188,000 adults.
The analysis of the data revealed that fibromyalgia was linked to a 27% greater risk of death from all causes.
Those with fibromyalgia were at a 44% greater risk of infections, including pneumonia. Their suicide risk was more than three times higher.
The greater risk of all-cause death could result from fatigue, poor sleep, and concentration problems, The BMJ said.
The patients had a 12% lower risk of dying from cancer, the analysis found. This could be because they tend to make more visits to health care professionals, the authors suggest.
“Fibromyalgia is often called an ‘imaginary condition,’ with ongoing debates on the legitimacy and clinical usefulness of this diagnosis. Our review provides further proof that fibromyalgia patients should be taken seriously, with particular focus on screening for suicidal ideation, prevention of accidents, and prevention and treatment of infections,” the researchers say.
A version of this article appeared on WebMD.com.
Mixed bag: New performance data on femoral-popliteal artery revascularization
Measured one way, success for peripheral vascular intervention (PVI) in the femoropopliteal arteries for patients with intermittent claudication has improved, as the need for repeat PVI appears to be very low, and lower than in recent years, a new analysis suggests. But measured another way, the researchers said, PVI’s record of success in peripheral arterial disease (PAD) remains marred by a substantial risk for amputation involving the treated limb.
In their analysis, The rate for popliteal interventions was significantly higher than for PVI limited to the superficial femoral artery (SFA), 7.5% and 3.4%, respectively.
The 4-year rate of repeat target-vessel revascularization, however, was “lower than expected” at 15.2% in the analysis, which was based on the PINC AI Healthcare Data database covering over 1,100 U.S. hospitals. The study was published online in JACC: Cardiovascular Interventions.
The amputation rates for index treated limbs “surprised us,” lead author S. Elissa Altin, MD, Yale University, New Haven, Conn., said in an interview. The increased rate after procedures limited to the popliteal artery, compared with the SFA, “were even more concerning,” she said. “This is higher than accepted natural history rates of amputation in patients with conservatively managed claudication.”
Of particular concern in the study, agreed the author of an accompanying editorial, “is the finding of a 1 in 25 risk for amputation among patients with [intermittent claudication] undergoing revascularization, which underscores that both patients and physicians must ensure that evidence-based lifestyle and medical therapies are exhausted prior to pursuing [femoropopliteal] revascularization.”
Given such amputation concerns “and the availability of effective lifestyle and medical therapies,” wrote Debabrata Mukherjee, MD, Texas Tech University Health Sciences Center, El Paso, “PVI should be restricted in stable PAD only for those with persistent lifestyle-limiting claudication despite [guideline-directed medical therapy] and structured exercise therapy.”
Dr. Altin and colleagues analyzed data from 19,324 patients with intermittent claudication (mean age, 69 years; 59% men) who underwent femoropopliteal PVI from 2016 to 2020.
Use of atherectomy and of drug-eluting balloons were both similarly prevalent for popliteal and SFA target arteries; however, SFA lesions were more commonly treated with stents.
The rate of amputation in the treated limb over 4 years was 4.3%; the rate of major (above the ankle) amputation was 3.2%.
The multivariable-adjusted treated-limb amputation hazard ratio for popliteal versus SFA procedures was for 2.10 (95% confidence interval, 1.52-2.92) for any amputation and 1.98 (95% CI, 1.32-2.95) for major amputation.
The 4-year rate of index-limb repeat revascularization was 16.7% overall, 20.1% for patients with an index procedure in both the popliteal and SFA segments, 19% after popliteal-only procedures, and 15.4% after SFA-only procedures (P < .0001), the report stated.
The overall lower-than-expected revascularization rates, the authors proposed, may reflect improvements in endovascular therapies for femoropopliteal lesions, such as drug-eluting stents and advances in medical therapy.
“Additionally, this may underscore a difference between trial-defined target-lesion revascularization compared with clinically driven target-lesion revascularization in practice,” they wrote.
The study’s revascularization rates could have been underestimated because “some of the patients in this study may have had procedures conducted in other hospital systems or at an office-based lab during the study period,” proposed interventional cardiologist Seyi Bolorunduro MD, MPH, INOVA Heart and Vascular Institute, Falls Church, Va.
“This and other studies highlight the need to be cautious about offering PVI to patients with intermittent claudication,” said Dr. Bolorunduro, who was not connected with the current study. On the other hand, he added, randomized trial data show “that combination therapy with PVI followed by supervised exercise results in greater improvement in walking distances and quality-of-life scores, compared with supervised exercise alone, at 1 year.’
Femoropopliteal PVI “is an important tool for patients with residual, truly lifestyle-limiting claudication after exhausting medical therapies, complete smoking cessation, and structured exercise programs,” Dr. Altin said. Future studies, she added, should look prospectively at patients with claudication who underwent early versus delayed invasive management.
In his editorial, Dr. Mukherjee said that, for patients with PAD and claudication, a proprotein convertase subtilisin/kexin type 9 inhibitor may be recommended if LDL cholesterol remains 70 mg/dL or higher and symptoms persist after a regimen of lifestyle modification, exercise, antiplatelet therapy, and high-intensity statins and other guideline-directed medical therapy. He also suggests a direct oral anticoagulant be considered before resorting to endovascular or surgical revascularization.
“We need to optimize risk-factor modification, medical therapy and exercise, and only reserve PVI for patients with severe lifestyle-limiting intermittent claudication who have tried and failed everything else,” Dr. Bolorunduro agreed in an interview. “I educate my patients about [the amputation] risk and let them know that PVI is not a panacea.”
Dr. Altin has disclosed no relevant relationships. Dr. Mukherjee and Dr. Bolorunduro have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Measured one way, success for peripheral vascular intervention (PVI) in the femoropopliteal arteries for patients with intermittent claudication has improved, as the need for repeat PVI appears to be very low, and lower than in recent years, a new analysis suggests. But measured another way, the researchers said, PVI’s record of success in peripheral arterial disease (PAD) remains marred by a substantial risk for amputation involving the treated limb.
In their analysis, The rate for popliteal interventions was significantly higher than for PVI limited to the superficial femoral artery (SFA), 7.5% and 3.4%, respectively.
The 4-year rate of repeat target-vessel revascularization, however, was “lower than expected” at 15.2% in the analysis, which was based on the PINC AI Healthcare Data database covering over 1,100 U.S. hospitals. The study was published online in JACC: Cardiovascular Interventions.
The amputation rates for index treated limbs “surprised us,” lead author S. Elissa Altin, MD, Yale University, New Haven, Conn., said in an interview. The increased rate after procedures limited to the popliteal artery, compared with the SFA, “were even more concerning,” she said. “This is higher than accepted natural history rates of amputation in patients with conservatively managed claudication.”
Of particular concern in the study, agreed the author of an accompanying editorial, “is the finding of a 1 in 25 risk for amputation among patients with [intermittent claudication] undergoing revascularization, which underscores that both patients and physicians must ensure that evidence-based lifestyle and medical therapies are exhausted prior to pursuing [femoropopliteal] revascularization.”
Given such amputation concerns “and the availability of effective lifestyle and medical therapies,” wrote Debabrata Mukherjee, MD, Texas Tech University Health Sciences Center, El Paso, “PVI should be restricted in stable PAD only for those with persistent lifestyle-limiting claudication despite [guideline-directed medical therapy] and structured exercise therapy.”
Dr. Altin and colleagues analyzed data from 19,324 patients with intermittent claudication (mean age, 69 years; 59% men) who underwent femoropopliteal PVI from 2016 to 2020.
Use of atherectomy and of drug-eluting balloons were both similarly prevalent for popliteal and SFA target arteries; however, SFA lesions were more commonly treated with stents.
The rate of amputation in the treated limb over 4 years was 4.3%; the rate of major (above the ankle) amputation was 3.2%.
The multivariable-adjusted treated-limb amputation hazard ratio for popliteal versus SFA procedures was for 2.10 (95% confidence interval, 1.52-2.92) for any amputation and 1.98 (95% CI, 1.32-2.95) for major amputation.
The 4-year rate of index-limb repeat revascularization was 16.7% overall, 20.1% for patients with an index procedure in both the popliteal and SFA segments, 19% after popliteal-only procedures, and 15.4% after SFA-only procedures (P < .0001), the report stated.
The overall lower-than-expected revascularization rates, the authors proposed, may reflect improvements in endovascular therapies for femoropopliteal lesions, such as drug-eluting stents and advances in medical therapy.
“Additionally, this may underscore a difference between trial-defined target-lesion revascularization compared with clinically driven target-lesion revascularization in practice,” they wrote.
The study’s revascularization rates could have been underestimated because “some of the patients in this study may have had procedures conducted in other hospital systems or at an office-based lab during the study period,” proposed interventional cardiologist Seyi Bolorunduro MD, MPH, INOVA Heart and Vascular Institute, Falls Church, Va.
“This and other studies highlight the need to be cautious about offering PVI to patients with intermittent claudication,” said Dr. Bolorunduro, who was not connected with the current study. On the other hand, he added, randomized trial data show “that combination therapy with PVI followed by supervised exercise results in greater improvement in walking distances and quality-of-life scores, compared with supervised exercise alone, at 1 year.’
Femoropopliteal PVI “is an important tool for patients with residual, truly lifestyle-limiting claudication after exhausting medical therapies, complete smoking cessation, and structured exercise programs,” Dr. Altin said. Future studies, she added, should look prospectively at patients with claudication who underwent early versus delayed invasive management.
In his editorial, Dr. Mukherjee said that, for patients with PAD and claudication, a proprotein convertase subtilisin/kexin type 9 inhibitor may be recommended if LDL cholesterol remains 70 mg/dL or higher and symptoms persist after a regimen of lifestyle modification, exercise, antiplatelet therapy, and high-intensity statins and other guideline-directed medical therapy. He also suggests a direct oral anticoagulant be considered before resorting to endovascular or surgical revascularization.
“We need to optimize risk-factor modification, medical therapy and exercise, and only reserve PVI for patients with severe lifestyle-limiting intermittent claudication who have tried and failed everything else,” Dr. Bolorunduro agreed in an interview. “I educate my patients about [the amputation] risk and let them know that PVI is not a panacea.”
Dr. Altin has disclosed no relevant relationships. Dr. Mukherjee and Dr. Bolorunduro have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Measured one way, success for peripheral vascular intervention (PVI) in the femoropopliteal arteries for patients with intermittent claudication has improved, as the need for repeat PVI appears to be very low, and lower than in recent years, a new analysis suggests. But measured another way, the researchers said, PVI’s record of success in peripheral arterial disease (PAD) remains marred by a substantial risk for amputation involving the treated limb.
In their analysis, The rate for popliteal interventions was significantly higher than for PVI limited to the superficial femoral artery (SFA), 7.5% and 3.4%, respectively.
The 4-year rate of repeat target-vessel revascularization, however, was “lower than expected” at 15.2% in the analysis, which was based on the PINC AI Healthcare Data database covering over 1,100 U.S. hospitals. The study was published online in JACC: Cardiovascular Interventions.
The amputation rates for index treated limbs “surprised us,” lead author S. Elissa Altin, MD, Yale University, New Haven, Conn., said in an interview. The increased rate after procedures limited to the popliteal artery, compared with the SFA, “were even more concerning,” she said. “This is higher than accepted natural history rates of amputation in patients with conservatively managed claudication.”
Of particular concern in the study, agreed the author of an accompanying editorial, “is the finding of a 1 in 25 risk for amputation among patients with [intermittent claudication] undergoing revascularization, which underscores that both patients and physicians must ensure that evidence-based lifestyle and medical therapies are exhausted prior to pursuing [femoropopliteal] revascularization.”
Given such amputation concerns “and the availability of effective lifestyle and medical therapies,” wrote Debabrata Mukherjee, MD, Texas Tech University Health Sciences Center, El Paso, “PVI should be restricted in stable PAD only for those with persistent lifestyle-limiting claudication despite [guideline-directed medical therapy] and structured exercise therapy.”
Dr. Altin and colleagues analyzed data from 19,324 patients with intermittent claudication (mean age, 69 years; 59% men) who underwent femoropopliteal PVI from 2016 to 2020.
Use of atherectomy and of drug-eluting balloons were both similarly prevalent for popliteal and SFA target arteries; however, SFA lesions were more commonly treated with stents.
The rate of amputation in the treated limb over 4 years was 4.3%; the rate of major (above the ankle) amputation was 3.2%.
The multivariable-adjusted treated-limb amputation hazard ratio for popliteal versus SFA procedures was for 2.10 (95% confidence interval, 1.52-2.92) for any amputation and 1.98 (95% CI, 1.32-2.95) for major amputation.
The 4-year rate of index-limb repeat revascularization was 16.7% overall, 20.1% for patients with an index procedure in both the popliteal and SFA segments, 19% after popliteal-only procedures, and 15.4% after SFA-only procedures (P < .0001), the report stated.
The overall lower-than-expected revascularization rates, the authors proposed, may reflect improvements in endovascular therapies for femoropopliteal lesions, such as drug-eluting stents and advances in medical therapy.
“Additionally, this may underscore a difference between trial-defined target-lesion revascularization compared with clinically driven target-lesion revascularization in practice,” they wrote.
The study’s revascularization rates could have been underestimated because “some of the patients in this study may have had procedures conducted in other hospital systems or at an office-based lab during the study period,” proposed interventional cardiologist Seyi Bolorunduro MD, MPH, INOVA Heart and Vascular Institute, Falls Church, Va.
“This and other studies highlight the need to be cautious about offering PVI to patients with intermittent claudication,” said Dr. Bolorunduro, who was not connected with the current study. On the other hand, he added, randomized trial data show “that combination therapy with PVI followed by supervised exercise results in greater improvement in walking distances and quality-of-life scores, compared with supervised exercise alone, at 1 year.’
Femoropopliteal PVI “is an important tool for patients with residual, truly lifestyle-limiting claudication after exhausting medical therapies, complete smoking cessation, and structured exercise programs,” Dr. Altin said. Future studies, she added, should look prospectively at patients with claudication who underwent early versus delayed invasive management.
In his editorial, Dr. Mukherjee said that, for patients with PAD and claudication, a proprotein convertase subtilisin/kexin type 9 inhibitor may be recommended if LDL cholesterol remains 70 mg/dL or higher and symptoms persist after a regimen of lifestyle modification, exercise, antiplatelet therapy, and high-intensity statins and other guideline-directed medical therapy. He also suggests a direct oral anticoagulant be considered before resorting to endovascular or surgical revascularization.
“We need to optimize risk-factor modification, medical therapy and exercise, and only reserve PVI for patients with severe lifestyle-limiting intermittent claudication who have tried and failed everything else,” Dr. Bolorunduro agreed in an interview. “I educate my patients about [the amputation] risk and let them know that PVI is not a panacea.”
Dr. Altin has disclosed no relevant relationships. Dr. Mukherjee and Dr. Bolorunduro have no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
What's your diagnosis?
The diagnosis
Based on the clinical and imaging findings, a diagnosis of gallbladder adenomyomatosis was made. GA is a benign and usually asymptomatic condition that occurs mainly beyond the age of 50-60 years and is very rare in childhood.1 Symptomatic gallbladder adenomyomatosis indicates cholecystectomy, considering the presence of inflammation or gallbladder stones.2 Therefore, a laparoscopic cholecystectomy was performed on our patient. Rokitansky-Aschoff sinuses were seen in the entire thickened gallbladder wall on gross pathologic examination (Figure D). Histopathologic examination confirmed the diagnosis of GA with cholecystitis. The patient was eventually diagnosed with diffuse GA. She was successfully discharged from the hospital 4 days after surgery, and 3 months of follow-up were uneventful.
References
Eroglu N et al. Diffuse adenomyomatosis of the gallbladder in a child. J Pediatr Hematol Oncol. 2016;38:e307-9.
Bonatti M. et al. Gallbladder adenomyomatosis: imaging findings, tricks and pitfalls. Insights Imaging. 2017;8:243-53.
Hammad AY et al. A literature review of radiological findings to guide the diagnosis of gallbladder adenomyomatosis. HPB (Oxford). 2016;18:129-35.
The diagnosis
Based on the clinical and imaging findings, a diagnosis of gallbladder adenomyomatosis was made. GA is a benign and usually asymptomatic condition that occurs mainly beyond the age of 50-60 years and is very rare in childhood.1 Symptomatic gallbladder adenomyomatosis indicates cholecystectomy, considering the presence of inflammation or gallbladder stones.2 Therefore, a laparoscopic cholecystectomy was performed on our patient. Rokitansky-Aschoff sinuses were seen in the entire thickened gallbladder wall on gross pathologic examination (Figure D). Histopathologic examination confirmed the diagnosis of GA with cholecystitis. The patient was eventually diagnosed with diffuse GA. She was successfully discharged from the hospital 4 days after surgery, and 3 months of follow-up were uneventful.
References
Eroglu N et al. Diffuse adenomyomatosis of the gallbladder in a child. J Pediatr Hematol Oncol. 2016;38:e307-9.
Bonatti M. et al. Gallbladder adenomyomatosis: imaging findings, tricks and pitfalls. Insights Imaging. 2017;8:243-53.
Hammad AY et al. A literature review of radiological findings to guide the diagnosis of gallbladder adenomyomatosis. HPB (Oxford). 2016;18:129-35.
The diagnosis
Based on the clinical and imaging findings, a diagnosis of gallbladder adenomyomatosis was made. GA is a benign and usually asymptomatic condition that occurs mainly beyond the age of 50-60 years and is very rare in childhood.1 Symptomatic gallbladder adenomyomatosis indicates cholecystectomy, considering the presence of inflammation or gallbladder stones.2 Therefore, a laparoscopic cholecystectomy was performed on our patient. Rokitansky-Aschoff sinuses were seen in the entire thickened gallbladder wall on gross pathologic examination (Figure D). Histopathologic examination confirmed the diagnosis of GA with cholecystitis. The patient was eventually diagnosed with diffuse GA. She was successfully discharged from the hospital 4 days after surgery, and 3 months of follow-up were uneventful.
References
Eroglu N et al. Diffuse adenomyomatosis of the gallbladder in a child. J Pediatr Hematol Oncol. 2016;38:e307-9.
Bonatti M. et al. Gallbladder adenomyomatosis: imaging findings, tricks and pitfalls. Insights Imaging. 2017;8:243-53.
Hammad AY et al. A literature review of radiological findings to guide the diagnosis of gallbladder adenomyomatosis. HPB (Oxford). 2016;18:129-35.
A 15-year-old girl presented with an 18-month history of intermittent right upper quadrant pain that appeared after meals and was relieved after rest. She denied any nausea, vomiting, chills, diarrhea, or constipation. The patient reported no trauma. At admission, physical examination showed tenderness in the right upper abdomen without rebound or guarding. Murphy's sign was also present. The laboratory tests were unremarkable.
Ultrasound examination indicated gallbladder wall thickening. Furthermore, a contrast-enhanced computed tomographic scan showed marked gallbladder wall thickening with an annular unenhanced proliferative muscularis layer surrounding enhanced proliferative mucosal epithelium (Figure A), and magnetic resonance imaging showed multiple cyst-like spaces in the gallbladder wall (Figures B and C).
What is the diagnosis, and how should it be managed?
Previously published in Gastroenterology
Celiac disease: Update on diagnosis and monitoring
Celiac disease is a small bowel disorder. Specific antibodies along with a duodenal biopsy allow a secure diagnosis of celiac disease. Case detection rates have improved but many patients remain undiagnosed.
The only treatment available at present is a gluten-free diet (GFD). Most patients respond clinically to a GFD but histologic recovery is not always complete and may result in clinical consequences.
The anti-tissue transglutaminase IgA test (tTg-IgA) is the best initial serology test. A total IgA level appropriate for age is required to interpret a negative result. In patients with IgA deficiency, the deamidated gliadin peptide (DGP) antibodies, and/or tTg-IgA, may be helpful for diagnosis along with a duodenal biopsy.
First-degree female relatives with homozygous DQ2 positivity are at highest risk.
Both serology and duodenal biopsy have pitfalls in the diagnosis of celiac disease. In children, the diagnosis is secure with a tTg-IgA rate of at least 10 times the upper limit of normal (≥10×ULN) with positive endomysial antibodies (EMA).
There is less data on the correlation of tTg-IgA ≥10×ULN positive with villous atrophy in adults. All others require biopsy for diagnosis.
Considerations to forgo biopsy in adults include: tTg-IgA of ≥10×ULN positive, serology positive test in patients following GFD, or otherwise unable to undergo endoscopy with duodenal biopsy, or shared decision-making. Celiac disease recovery is assessed by clinical response to a GFD and antibody conversion to negative, which does not always correlate with histology.
Clinical consequences of persistent villous atrophy include increased risks for lymphoproliferative malignancy, hip fracture, and refractory celiac disease.
Dr. Semrad is director of the small bowel disease and nutrition program at the University of Chicago Medicine where she is a professor of medicine. She disclosed no conflicts of interest.
References
Rubio-Tapia et al. Am J Gastroenterol. 2023;118:59-76.
Husby S et al. J Pediatr Gastroenterol Nutr. 2020;70:141-57.
Celiac disease is a small bowel disorder. Specific antibodies along with a duodenal biopsy allow a secure diagnosis of celiac disease. Case detection rates have improved but many patients remain undiagnosed.
The only treatment available at present is a gluten-free diet (GFD). Most patients respond clinically to a GFD but histologic recovery is not always complete and may result in clinical consequences.
The anti-tissue transglutaminase IgA test (tTg-IgA) is the best initial serology test. A total IgA level appropriate for age is required to interpret a negative result. In patients with IgA deficiency, the deamidated gliadin peptide (DGP) antibodies, and/or tTg-IgA, may be helpful for diagnosis along with a duodenal biopsy.
First-degree female relatives with homozygous DQ2 positivity are at highest risk.
Both serology and duodenal biopsy have pitfalls in the diagnosis of celiac disease. In children, the diagnosis is secure with a tTg-IgA rate of at least 10 times the upper limit of normal (≥10×ULN) with positive endomysial antibodies (EMA).
There is less data on the correlation of tTg-IgA ≥10×ULN positive with villous atrophy in adults. All others require biopsy for diagnosis.
Considerations to forgo biopsy in adults include: tTg-IgA of ≥10×ULN positive, serology positive test in patients following GFD, or otherwise unable to undergo endoscopy with duodenal biopsy, or shared decision-making. Celiac disease recovery is assessed by clinical response to a GFD and antibody conversion to negative, which does not always correlate with histology.
Clinical consequences of persistent villous atrophy include increased risks for lymphoproliferative malignancy, hip fracture, and refractory celiac disease.
Dr. Semrad is director of the small bowel disease and nutrition program at the University of Chicago Medicine where she is a professor of medicine. She disclosed no conflicts of interest.
References
Rubio-Tapia et al. Am J Gastroenterol. 2023;118:59-76.
Husby S et al. J Pediatr Gastroenterol Nutr. 2020;70:141-57.
Celiac disease is a small bowel disorder. Specific antibodies along with a duodenal biopsy allow a secure diagnosis of celiac disease. Case detection rates have improved but many patients remain undiagnosed.
The only treatment available at present is a gluten-free diet (GFD). Most patients respond clinically to a GFD but histologic recovery is not always complete and may result in clinical consequences.
The anti-tissue transglutaminase IgA test (tTg-IgA) is the best initial serology test. A total IgA level appropriate for age is required to interpret a negative result. In patients with IgA deficiency, the deamidated gliadin peptide (DGP) antibodies, and/or tTg-IgA, may be helpful for diagnosis along with a duodenal biopsy.
First-degree female relatives with homozygous DQ2 positivity are at highest risk.
Both serology and duodenal biopsy have pitfalls in the diagnosis of celiac disease. In children, the diagnosis is secure with a tTg-IgA rate of at least 10 times the upper limit of normal (≥10×ULN) with positive endomysial antibodies (EMA).
There is less data on the correlation of tTg-IgA ≥10×ULN positive with villous atrophy in adults. All others require biopsy for diagnosis.
Considerations to forgo biopsy in adults include: tTg-IgA of ≥10×ULN positive, serology positive test in patients following GFD, or otherwise unable to undergo endoscopy with duodenal biopsy, or shared decision-making. Celiac disease recovery is assessed by clinical response to a GFD and antibody conversion to negative, which does not always correlate with histology.
Clinical consequences of persistent villous atrophy include increased risks for lymphoproliferative malignancy, hip fracture, and refractory celiac disease.
Dr. Semrad is director of the small bowel disease and nutrition program at the University of Chicago Medicine where she is a professor of medicine. She disclosed no conflicts of interest.
References
Rubio-Tapia et al. Am J Gastroenterol. 2023;118:59-76.
Husby S et al. J Pediatr Gastroenterol Nutr. 2020;70:141-57.