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FDA warns of possible cancer risk with lorcaserin
after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.
“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.
The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.
“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.
Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.
Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.
Lorcaserin is distributed by Eisai.*
*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin.
after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.
“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.
The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.
“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.
Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.
Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.
Lorcaserin is distributed by Eisai.*
*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin.
after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.
“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.
The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.
“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.
Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.
Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.
Lorcaserin is distributed by Eisai.*
*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin.
SPRINT-type BP control provides up to 3 years of additional life
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
REPORTING FROM AHA 2019
Expedited review programs not shortening drug development
Drug development times are not showing any signs of decreasing even though application review times at the Food and Drug Administration are improving, new research has shown.
“Despite the accumulation of expedited programs that have reduced FDA review times, overall clinical development times have not become shorter, although it is not possible to know what role these programs may have played in preventing an increase in development times,” Jonathan Darrow of Harvard Medical School, Boston, and colleagues wrote in a study published Jan. 14 in JAMA.
Researchers noted that FDA approval times declined from more than 3 years in 1983 to less than 1 year in 2017, although total time from the authorization of clinical testing to approval has remained steady across that period at about 8 years.
“The resistance of total development times to efforts to shorten them could be the result of more submissions of applications for rare disease drugs, which can sometimes pose trial recruitment challenges; a shifting emphasis to more challenging therapeutic categories, such as central nervous system disorder treatments; longer time horizons needed to establish efficacy when early intervention is important (e.g., cancer); or other factors,” wrote Mr. Darrow and colleagues.
The authors also note that the value of the expanded review toolbox the FDA now employs is “unclear” as “the number of new drug approvals has not increased substantially over the past three decades.” This observation does not count biologics or generic approvals.
Research revealed that the mean annual number of new drug approvals (including biologics) was 34 from 1990 to 1999, 25 from 2000 to 2009, and 41 from 2010 to 2018. In addition, while the number of new drug approvals has remained at or below 60 per year, the portion of drugs using at least one expedited review program increased over time, with more than 80% of the 59 new drugs approved in 2018 being subject to at least one expedited review program.
“Although the FDA has on average applied its expedited programs to drugs offering larger health gains, it is difficult to assess whether these programs have incentivized greater therapeutic innovation or merely allowed more appropriate agency prioritization,” noted Mr. Darrow and colleagues.
And while it may be hard to truly understand the impact of the many expedited review programs that have been introduced at the FDA, there is still room for improvement in the process.
In an editorial published in JAMA, Joshua Sharfstein, MD, of Johns Hopkins University, Baltimore, suggested four reforms the FDA could examine.
“First, Congress and the FDA should rationalize the various programs for expedited review,” he wrote, noting that companies are using the Orphan Drug Act to prevent competition. “Fixing the system requires, at a minimum, promoting meaningful competition for non-orphan uses.”
Second, he wrote, the FDA needs to strengthen oversight of postmarket safety though more diligence in the operation of its Risk Evaluation and Management Strategies (REMS) program.
“Third, Congress should recalibrate the programs that provide companies with special marketing protections,” added Dr. Sharfstein, former FDA principal deputy commissioner. “One place to look is pediatric exclusivity, which has been estimated to cost the health care system more than $6 for every $1 spent by a company on a pediatric trial.”
And finally, “Congress should use patent and pricing incentives to accelerate the generation of definitive evidence under accelerated approval,” citing proposals to limit pricing or market exclusivity until companies complete studies that assess clinically relevant endpoints.
“These changes would reflect an evolution, not a revolution, of the FDA’s approach to new drug approval,” Dr. Sharfstein said. “These reforms could also bring greater order and thoughtfulness to the regulation of important new therapies, while enhancing safety and creating greater capability to afford truly transformative medical products.”
SOURCE: Jonathan Darrow et al. JAMA 2020 Jan 14. doi: 10.1001/jama.2019.20288.
Drug development times are not showing any signs of decreasing even though application review times at the Food and Drug Administration are improving, new research has shown.
“Despite the accumulation of expedited programs that have reduced FDA review times, overall clinical development times have not become shorter, although it is not possible to know what role these programs may have played in preventing an increase in development times,” Jonathan Darrow of Harvard Medical School, Boston, and colleagues wrote in a study published Jan. 14 in JAMA.
Researchers noted that FDA approval times declined from more than 3 years in 1983 to less than 1 year in 2017, although total time from the authorization of clinical testing to approval has remained steady across that period at about 8 years.
“The resistance of total development times to efforts to shorten them could be the result of more submissions of applications for rare disease drugs, which can sometimes pose trial recruitment challenges; a shifting emphasis to more challenging therapeutic categories, such as central nervous system disorder treatments; longer time horizons needed to establish efficacy when early intervention is important (e.g., cancer); or other factors,” wrote Mr. Darrow and colleagues.
The authors also note that the value of the expanded review toolbox the FDA now employs is “unclear” as “the number of new drug approvals has not increased substantially over the past three decades.” This observation does not count biologics or generic approvals.
Research revealed that the mean annual number of new drug approvals (including biologics) was 34 from 1990 to 1999, 25 from 2000 to 2009, and 41 from 2010 to 2018. In addition, while the number of new drug approvals has remained at or below 60 per year, the portion of drugs using at least one expedited review program increased over time, with more than 80% of the 59 new drugs approved in 2018 being subject to at least one expedited review program.
“Although the FDA has on average applied its expedited programs to drugs offering larger health gains, it is difficult to assess whether these programs have incentivized greater therapeutic innovation or merely allowed more appropriate agency prioritization,” noted Mr. Darrow and colleagues.
And while it may be hard to truly understand the impact of the many expedited review programs that have been introduced at the FDA, there is still room for improvement in the process.
In an editorial published in JAMA, Joshua Sharfstein, MD, of Johns Hopkins University, Baltimore, suggested four reforms the FDA could examine.
“First, Congress and the FDA should rationalize the various programs for expedited review,” he wrote, noting that companies are using the Orphan Drug Act to prevent competition. “Fixing the system requires, at a minimum, promoting meaningful competition for non-orphan uses.”
Second, he wrote, the FDA needs to strengthen oversight of postmarket safety though more diligence in the operation of its Risk Evaluation and Management Strategies (REMS) program.
“Third, Congress should recalibrate the programs that provide companies with special marketing protections,” added Dr. Sharfstein, former FDA principal deputy commissioner. “One place to look is pediatric exclusivity, which has been estimated to cost the health care system more than $6 for every $1 spent by a company on a pediatric trial.”
And finally, “Congress should use patent and pricing incentives to accelerate the generation of definitive evidence under accelerated approval,” citing proposals to limit pricing or market exclusivity until companies complete studies that assess clinically relevant endpoints.
“These changes would reflect an evolution, not a revolution, of the FDA’s approach to new drug approval,” Dr. Sharfstein said. “These reforms could also bring greater order and thoughtfulness to the regulation of important new therapies, while enhancing safety and creating greater capability to afford truly transformative medical products.”
SOURCE: Jonathan Darrow et al. JAMA 2020 Jan 14. doi: 10.1001/jama.2019.20288.
Drug development times are not showing any signs of decreasing even though application review times at the Food and Drug Administration are improving, new research has shown.
“Despite the accumulation of expedited programs that have reduced FDA review times, overall clinical development times have not become shorter, although it is not possible to know what role these programs may have played in preventing an increase in development times,” Jonathan Darrow of Harvard Medical School, Boston, and colleagues wrote in a study published Jan. 14 in JAMA.
Researchers noted that FDA approval times declined from more than 3 years in 1983 to less than 1 year in 2017, although total time from the authorization of clinical testing to approval has remained steady across that period at about 8 years.
“The resistance of total development times to efforts to shorten them could be the result of more submissions of applications for rare disease drugs, which can sometimes pose trial recruitment challenges; a shifting emphasis to more challenging therapeutic categories, such as central nervous system disorder treatments; longer time horizons needed to establish efficacy when early intervention is important (e.g., cancer); or other factors,” wrote Mr. Darrow and colleagues.
The authors also note that the value of the expanded review toolbox the FDA now employs is “unclear” as “the number of new drug approvals has not increased substantially over the past three decades.” This observation does not count biologics or generic approvals.
Research revealed that the mean annual number of new drug approvals (including biologics) was 34 from 1990 to 1999, 25 from 2000 to 2009, and 41 from 2010 to 2018. In addition, while the number of new drug approvals has remained at or below 60 per year, the portion of drugs using at least one expedited review program increased over time, with more than 80% of the 59 new drugs approved in 2018 being subject to at least one expedited review program.
“Although the FDA has on average applied its expedited programs to drugs offering larger health gains, it is difficult to assess whether these programs have incentivized greater therapeutic innovation or merely allowed more appropriate agency prioritization,” noted Mr. Darrow and colleagues.
And while it may be hard to truly understand the impact of the many expedited review programs that have been introduced at the FDA, there is still room for improvement in the process.
In an editorial published in JAMA, Joshua Sharfstein, MD, of Johns Hopkins University, Baltimore, suggested four reforms the FDA could examine.
“First, Congress and the FDA should rationalize the various programs for expedited review,” he wrote, noting that companies are using the Orphan Drug Act to prevent competition. “Fixing the system requires, at a minimum, promoting meaningful competition for non-orphan uses.”
Second, he wrote, the FDA needs to strengthen oversight of postmarket safety though more diligence in the operation of its Risk Evaluation and Management Strategies (REMS) program.
“Third, Congress should recalibrate the programs that provide companies with special marketing protections,” added Dr. Sharfstein, former FDA principal deputy commissioner. “One place to look is pediatric exclusivity, which has been estimated to cost the health care system more than $6 for every $1 spent by a company on a pediatric trial.”
And finally, “Congress should use patent and pricing incentives to accelerate the generation of definitive evidence under accelerated approval,” citing proposals to limit pricing or market exclusivity until companies complete studies that assess clinically relevant endpoints.
“These changes would reflect an evolution, not a revolution, of the FDA’s approach to new drug approval,” Dr. Sharfstein said. “These reforms could also bring greater order and thoughtfulness to the regulation of important new therapies, while enhancing safety and creating greater capability to afford truly transformative medical products.”
SOURCE: Jonathan Darrow et al. JAMA 2020 Jan 14. doi: 10.1001/jama.2019.20288.
FROM JAMA
APPRENTICE registry: Wide variation exists in acute pancreatitis treatment, outcomes
Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.
In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.
Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
Demographics and etiologies
The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.
The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).
The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.
In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).
In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).
“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
Management
Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.
Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).
However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.
This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.
“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.
Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.
However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.
Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.
Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
Outcomes
The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).
Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.
Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.
Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.
The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
Implications of the findings
Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.
Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.
The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.
The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.
Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.
“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.
The authors reported having no disclosures.
SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.
Share AGA GI Patient Center education to help your patients understand acute versus chronic pancreatitis, testing, treatment, and potential complications at https://www.gastro.org/
Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.
In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.
Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
Demographics and etiologies
The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.
The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).
The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.
In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).
In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).
“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
Management
Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.
Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).
However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.
This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.
“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.
Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.
However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.
Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.
Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
Outcomes
The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).
Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.
Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.
Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.
The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
Implications of the findings
Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.
Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.
The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.
The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.
Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.
“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.
The authors reported having no disclosures.
SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.
Share AGA GI Patient Center education to help your patients understand acute versus chronic pancreatitis, testing, treatment, and potential complications at https://www.gastro.org/
Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.
In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.
Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
Demographics and etiologies
The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.
The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).
The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.
In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).
In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).
“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
Management
Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.
Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).
However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.
This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.
“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.
Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.
However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.
Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.
Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
Outcomes
The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).
Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.
Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.
Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.
The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
Implications of the findings
Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.
Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.
The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.
The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.
Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.
“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.
The authors reported having no disclosures.
SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.
Share AGA GI Patient Center education to help your patients understand acute versus chronic pancreatitis, testing, treatment, and potential complications at https://www.gastro.org/
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Brown-Black Punctate Macule on the Left Palm
The Diagnosis: Talon Noir
Paring of the stratum corneum overlying the lesion revealed coagulated blood, leading to a diagnosis of talon noir. Talon noir, also known as calcaneal petechiae, is a benign lesion that is typically found on the heel of the foot or palm of the hand.1 To the naked eye, talon noir appears as a brown-black asymmetric macule often with an overlying callus. Dermatoscopic visualization reveals grouped, reddish-colored globules composed of intracorneal hemorrhages, often in a linear pattern without any disruption of the normal skin surface architecture.1,2
Talon noir is the product of shear stress and often is seen in individuals who participate in sports such as baseball, hockey, soccer, and football.1,3 Lateral shearing forces cause tearing of blood vessels within the papillary dermis, which leads to punctate papillary dermal hemorrhages and extravasation of blood into the epidermis, resulting in intracorneal hemorrhage.1,4 Talon noir lesions are completely asymptomatic and typically resolve without intervention within 2 to 3 weeks of discontinuation of the precipitating sport or trauma.4
Recognizing talon noir is important, as it can occasionally be mistaken for acral lentiginous melanoma junctional nevus, tinea nigra, or verruca vulgaris. Paring of a lesion that is suspicious for talon noir is a simple and important step for ruling out a more ominous diagnosis (ie, acral lentiginous melanoma). If paring reveals coagulated blood, then junctional nevus, acral lentiginous melanoma, and tinea nigra can be excluded from the differential diagnosis. To rule out verruca vulgaris, one must prove that there is no disruption of the normal skin architecture, which can be confirmed with dermatoscopic visualization. Verrucae characteristically cause disruption of normal skin architecture, and junctional nevi would reveal a pigment pattern on dermatoscopy. This case illustrates how simple bedside procedures—dermoscopy and paring—can reassure patients and caregivers of the benign nature of talon noir.
1. Googe AB, Schulmeier JS, Jackson AR, et al. Talon noir: paring can eliminate the need for biopsy. Postgrad Med J. 2014;90:730-731.
2. Lao M, Weissler A, Siegfried E. Talon noir. J Pediatr. 2013;163:919.
3. Ayres S, Mihan R. Calcaneal petechiae. Arch Dermatol. 1972;106:262.
4. Bender TW. Cutaneous manifestations of disease in athletes. Skinmed. 2003;2:34-40
The Diagnosis: Talon Noir
Paring of the stratum corneum overlying the lesion revealed coagulated blood, leading to a diagnosis of talon noir. Talon noir, also known as calcaneal petechiae, is a benign lesion that is typically found on the heel of the foot or palm of the hand.1 To the naked eye, talon noir appears as a brown-black asymmetric macule often with an overlying callus. Dermatoscopic visualization reveals grouped, reddish-colored globules composed of intracorneal hemorrhages, often in a linear pattern without any disruption of the normal skin surface architecture.1,2
Talon noir is the product of shear stress and often is seen in individuals who participate in sports such as baseball, hockey, soccer, and football.1,3 Lateral shearing forces cause tearing of blood vessels within the papillary dermis, which leads to punctate papillary dermal hemorrhages and extravasation of blood into the epidermis, resulting in intracorneal hemorrhage.1,4 Talon noir lesions are completely asymptomatic and typically resolve without intervention within 2 to 3 weeks of discontinuation of the precipitating sport or trauma.4
Recognizing talon noir is important, as it can occasionally be mistaken for acral lentiginous melanoma junctional nevus, tinea nigra, or verruca vulgaris. Paring of a lesion that is suspicious for talon noir is a simple and important step for ruling out a more ominous diagnosis (ie, acral lentiginous melanoma). If paring reveals coagulated blood, then junctional nevus, acral lentiginous melanoma, and tinea nigra can be excluded from the differential diagnosis. To rule out verruca vulgaris, one must prove that there is no disruption of the normal skin architecture, which can be confirmed with dermatoscopic visualization. Verrucae characteristically cause disruption of normal skin architecture, and junctional nevi would reveal a pigment pattern on dermatoscopy. This case illustrates how simple bedside procedures—dermoscopy and paring—can reassure patients and caregivers of the benign nature of talon noir.
The Diagnosis: Talon Noir
Paring of the stratum corneum overlying the lesion revealed coagulated blood, leading to a diagnosis of talon noir. Talon noir, also known as calcaneal petechiae, is a benign lesion that is typically found on the heel of the foot or palm of the hand.1 To the naked eye, talon noir appears as a brown-black asymmetric macule often with an overlying callus. Dermatoscopic visualization reveals grouped, reddish-colored globules composed of intracorneal hemorrhages, often in a linear pattern without any disruption of the normal skin surface architecture.1,2
Talon noir is the product of shear stress and often is seen in individuals who participate in sports such as baseball, hockey, soccer, and football.1,3 Lateral shearing forces cause tearing of blood vessels within the papillary dermis, which leads to punctate papillary dermal hemorrhages and extravasation of blood into the epidermis, resulting in intracorneal hemorrhage.1,4 Talon noir lesions are completely asymptomatic and typically resolve without intervention within 2 to 3 weeks of discontinuation of the precipitating sport or trauma.4
Recognizing talon noir is important, as it can occasionally be mistaken for acral lentiginous melanoma junctional nevus, tinea nigra, or verruca vulgaris. Paring of a lesion that is suspicious for talon noir is a simple and important step for ruling out a more ominous diagnosis (ie, acral lentiginous melanoma). If paring reveals coagulated blood, then junctional nevus, acral lentiginous melanoma, and tinea nigra can be excluded from the differential diagnosis. To rule out verruca vulgaris, one must prove that there is no disruption of the normal skin architecture, which can be confirmed with dermatoscopic visualization. Verrucae characteristically cause disruption of normal skin architecture, and junctional nevi would reveal a pigment pattern on dermatoscopy. This case illustrates how simple bedside procedures—dermoscopy and paring—can reassure patients and caregivers of the benign nature of talon noir.
1. Googe AB, Schulmeier JS, Jackson AR, et al. Talon noir: paring can eliminate the need for biopsy. Postgrad Med J. 2014;90:730-731.
2. Lao M, Weissler A, Siegfried E. Talon noir. J Pediatr. 2013;163:919.
3. Ayres S, Mihan R. Calcaneal petechiae. Arch Dermatol. 1972;106:262.
4. Bender TW. Cutaneous manifestations of disease in athletes. Skinmed. 2003;2:34-40
1. Googe AB, Schulmeier JS, Jackson AR, et al. Talon noir: paring can eliminate the need for biopsy. Postgrad Med J. 2014;90:730-731.
2. Lao M, Weissler A, Siegfried E. Talon noir. J Pediatr. 2013;163:919.
3. Ayres S, Mihan R. Calcaneal petechiae. Arch Dermatol. 1972;106:262.
4. Bender TW. Cutaneous manifestations of disease in athletes. Skinmed. 2003;2:34-40
A 16-year-old adolescent boy presented to our clinic with a “new brown mole” on the left palm that had appeared within the last few months. The patient did not recall if it had changed in size, shape, or color, and there was no associated pain or itching. He denied any trauma to the hand, but he actively played both hockey and baseball. Physical examination revealed calloused palms bilaterally. One of the calluses was present over the hypothenar eminence, and centrally there were grouped brown-black punctate macules, some that coalesced into larger macules. Dermatoscopic examination (inset) revealed punctate rustcolored macules in a parallel ridge pattern. There was no disruption of the normal skin architecture.
APPRENTICE registry: Wide variation exists in acute pancreatitis treatment, outcomes
Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.
In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.
Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
Demographics and etiologies
The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.
The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).
The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.
In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).
In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).
“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
Management
Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.
Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).
However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.
This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.
“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.
Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.
However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.
Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.
Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
Outcomes
The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).
Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.
Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.
Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.
The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
Implications of the findings
Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.
Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.
The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.
The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.
Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.
“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.
The authors reported having no disclosures.
SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.
Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.
In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.
Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
Demographics and etiologies
The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.
The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).
The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.
In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).
In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).
“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
Management
Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.
Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).
However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.
This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.
“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.
Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.
However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.
Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.
Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
Outcomes
The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).
Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.
Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.
Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.
The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
Implications of the findings
Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.
Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.
The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.
The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.
Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.
“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.
The authors reported having no disclosures.
SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.
Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.
In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.
Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
Demographics and etiologies
The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.
The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).
The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.
In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).
In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).
“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
Management
Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.
Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).
However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.
This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.
“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.
Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.
However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.
Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.
Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
Outcomes
The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).
Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.
Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.
Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.
The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
Implications of the findings
Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.
Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.
The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.
The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.
Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.
“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.
The authors reported having no disclosures.
SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Consider sparing the uterus in prolapse procedures
LAS VEGAS – A female pelvic medicine and reconstructive surgeon urged colleagues to consider uterus-sparing hysteropexies instead of hysterectomies in pelvic organ prolapse repairs.
said Beri M. Ridgeway, MD, of the Cleveland Clinic, at the Pelvic Anatomy and Gynecologic Surgery Symposium. Even so, “in the U.S., gynecologists rarely offer uterine preservation for women who desire repair of their uterovaginal prolapse.”
According to research compiled by Dr. Ridgeway, about 74,000 hysterectomies are performed each year in the United States to treat pelvic organ prolapse. The procedure became standard in the second half of the 20th century, in part to reduce cancer risk.
But attitudes evolved starting in the 1990s “as we have had better cancer screening and more focus on patient sexuality, patient autonomy, and quality of life,” Dr. Ridgeway said.
She offered these reasons to question hysterectomies to treat pelvic organ prolapse repairs:
- It’s not clear whether hysterectomies address the anatomic problems that produce prolapse in the first place. “Prolapse is caused by weakened or damaged tissue – connective tissue, muscles, etc.,” she said in an interview. “The problem is what is supporting the uterus, not the uterus itself.”
- Despite assumptions, women don’t necessarily prefer hysterectomy. Dr. Ridgeway pointed to a 2013 study in which researchers surveyed 213 women with prolapse symptoms about their preferred treatment, assuming that outcomes were the same. The results: 36% preferred uterine preservation, 20% preferred hysterectomy, and 44% reported no strong preference (Am J Obstet Gynecol. 2013 Nov;209[5]:470.e1-6.).
- Hysterectomies hasten menopause.
There has been a perception that uterus removal is appropriate in women who don’t wish to have any more children, Dr. Ridgeway said. “You had your babies, you’re done, you don’t need this anymore.” In fact, “that’s basically not true.”
As she explained, hysterectomy is linked to earlier menopause, and “even losing one ovary pushed patients into menopause significantly earlier.” She pointed to a 2016 Australian study, which found that “women who have a hysterectomy (with ovarian conservation) have a higher risk of hot flushes and night sweats that persist over an extended period” (Maturitas. 2016 Sep;91:1-7).
There’s no consensus on how hysterectomy affects sexual function. However, Dr. Ridgeway noted, it’s clear that pelvic floor disorders disrupt sexual function, and most women see improvement after surgical treatment.
The rate of uterine pathology is low in hysterectomy. Dr. Ridgeway highlighted a 2018 study of 24,076 women who underwent hysterectomy for benign indications. The study reported that “prevalence of occult corpus uteri, cervical, and ovarian malignancy was 1.44%, 0.60%, and 0.19%, respectively, among women undergoing hysterectomy and it varied by patient age and surgical route” (Obstet Gynecol. 2018 Apr;131[4]:642-51).
As an alternative, Dr. Ridgeway pointed to hysteropexy, which can be performed as a vaginal, laparoscopic, robot, or open procedure.
She highlighted a 2018 systematic review of pelvic organ prolapse surgeries that provided a meta-analysis and clinical practice guidelines. It found that “uterine-preserving prolapse surgeries improve operating time, blood loss, and risk of mesh exposure, compared with similar surgical routes with concomitant hysterectomy and do not significantly change short-term prolapse outcomes” (Am J Obstet Gynecol. 2018 Aug;219[2]:129-46.e2).
Dr. Ridgeway reported no relevant disclosures. This meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
LAS VEGAS – A female pelvic medicine and reconstructive surgeon urged colleagues to consider uterus-sparing hysteropexies instead of hysterectomies in pelvic organ prolapse repairs.
said Beri M. Ridgeway, MD, of the Cleveland Clinic, at the Pelvic Anatomy and Gynecologic Surgery Symposium. Even so, “in the U.S., gynecologists rarely offer uterine preservation for women who desire repair of their uterovaginal prolapse.”
According to research compiled by Dr. Ridgeway, about 74,000 hysterectomies are performed each year in the United States to treat pelvic organ prolapse. The procedure became standard in the second half of the 20th century, in part to reduce cancer risk.
But attitudes evolved starting in the 1990s “as we have had better cancer screening and more focus on patient sexuality, patient autonomy, and quality of life,” Dr. Ridgeway said.
She offered these reasons to question hysterectomies to treat pelvic organ prolapse repairs:
- It’s not clear whether hysterectomies address the anatomic problems that produce prolapse in the first place. “Prolapse is caused by weakened or damaged tissue – connective tissue, muscles, etc.,” she said in an interview. “The problem is what is supporting the uterus, not the uterus itself.”
- Despite assumptions, women don’t necessarily prefer hysterectomy. Dr. Ridgeway pointed to a 2013 study in which researchers surveyed 213 women with prolapse symptoms about their preferred treatment, assuming that outcomes were the same. The results: 36% preferred uterine preservation, 20% preferred hysterectomy, and 44% reported no strong preference (Am J Obstet Gynecol. 2013 Nov;209[5]:470.e1-6.).
- Hysterectomies hasten menopause.
There has been a perception that uterus removal is appropriate in women who don’t wish to have any more children, Dr. Ridgeway said. “You had your babies, you’re done, you don’t need this anymore.” In fact, “that’s basically not true.”
As she explained, hysterectomy is linked to earlier menopause, and “even losing one ovary pushed patients into menopause significantly earlier.” She pointed to a 2016 Australian study, which found that “women who have a hysterectomy (with ovarian conservation) have a higher risk of hot flushes and night sweats that persist over an extended period” (Maturitas. 2016 Sep;91:1-7).
There’s no consensus on how hysterectomy affects sexual function. However, Dr. Ridgeway noted, it’s clear that pelvic floor disorders disrupt sexual function, and most women see improvement after surgical treatment.
The rate of uterine pathology is low in hysterectomy. Dr. Ridgeway highlighted a 2018 study of 24,076 women who underwent hysterectomy for benign indications. The study reported that “prevalence of occult corpus uteri, cervical, and ovarian malignancy was 1.44%, 0.60%, and 0.19%, respectively, among women undergoing hysterectomy and it varied by patient age and surgical route” (Obstet Gynecol. 2018 Apr;131[4]:642-51).
As an alternative, Dr. Ridgeway pointed to hysteropexy, which can be performed as a vaginal, laparoscopic, robot, or open procedure.
She highlighted a 2018 systematic review of pelvic organ prolapse surgeries that provided a meta-analysis and clinical practice guidelines. It found that “uterine-preserving prolapse surgeries improve operating time, blood loss, and risk of mesh exposure, compared with similar surgical routes with concomitant hysterectomy and do not significantly change short-term prolapse outcomes” (Am J Obstet Gynecol. 2018 Aug;219[2]:129-46.e2).
Dr. Ridgeway reported no relevant disclosures. This meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
LAS VEGAS – A female pelvic medicine and reconstructive surgeon urged colleagues to consider uterus-sparing hysteropexies instead of hysterectomies in pelvic organ prolapse repairs.
said Beri M. Ridgeway, MD, of the Cleveland Clinic, at the Pelvic Anatomy and Gynecologic Surgery Symposium. Even so, “in the U.S., gynecologists rarely offer uterine preservation for women who desire repair of their uterovaginal prolapse.”
According to research compiled by Dr. Ridgeway, about 74,000 hysterectomies are performed each year in the United States to treat pelvic organ prolapse. The procedure became standard in the second half of the 20th century, in part to reduce cancer risk.
But attitudes evolved starting in the 1990s “as we have had better cancer screening and more focus on patient sexuality, patient autonomy, and quality of life,” Dr. Ridgeway said.
She offered these reasons to question hysterectomies to treat pelvic organ prolapse repairs:
- It’s not clear whether hysterectomies address the anatomic problems that produce prolapse in the first place. “Prolapse is caused by weakened or damaged tissue – connective tissue, muscles, etc.,” she said in an interview. “The problem is what is supporting the uterus, not the uterus itself.”
- Despite assumptions, women don’t necessarily prefer hysterectomy. Dr. Ridgeway pointed to a 2013 study in which researchers surveyed 213 women with prolapse symptoms about their preferred treatment, assuming that outcomes were the same. The results: 36% preferred uterine preservation, 20% preferred hysterectomy, and 44% reported no strong preference (Am J Obstet Gynecol. 2013 Nov;209[5]:470.e1-6.).
- Hysterectomies hasten menopause.
There has been a perception that uterus removal is appropriate in women who don’t wish to have any more children, Dr. Ridgeway said. “You had your babies, you’re done, you don’t need this anymore.” In fact, “that’s basically not true.”
As she explained, hysterectomy is linked to earlier menopause, and “even losing one ovary pushed patients into menopause significantly earlier.” She pointed to a 2016 Australian study, which found that “women who have a hysterectomy (with ovarian conservation) have a higher risk of hot flushes and night sweats that persist over an extended period” (Maturitas. 2016 Sep;91:1-7).
There’s no consensus on how hysterectomy affects sexual function. However, Dr. Ridgeway noted, it’s clear that pelvic floor disorders disrupt sexual function, and most women see improvement after surgical treatment.
The rate of uterine pathology is low in hysterectomy. Dr. Ridgeway highlighted a 2018 study of 24,076 women who underwent hysterectomy for benign indications. The study reported that “prevalence of occult corpus uteri, cervical, and ovarian malignancy was 1.44%, 0.60%, and 0.19%, respectively, among women undergoing hysterectomy and it varied by patient age and surgical route” (Obstet Gynecol. 2018 Apr;131[4]:642-51).
As an alternative, Dr. Ridgeway pointed to hysteropexy, which can be performed as a vaginal, laparoscopic, robot, or open procedure.
She highlighted a 2018 systematic review of pelvic organ prolapse surgeries that provided a meta-analysis and clinical practice guidelines. It found that “uterine-preserving prolapse surgeries improve operating time, blood loss, and risk of mesh exposure, compared with similar surgical routes with concomitant hysterectomy and do not significantly change short-term prolapse outcomes” (Am J Obstet Gynecol. 2018 Aug;219[2]:129-46.e2).
Dr. Ridgeway reported no relevant disclosures. This meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
EXPERT ANALYSIS FROM PAGS 2019
Chemo-free induction-consolidation protocol for Ph+ ALL improved survival
ORLANDO – A front-line chemotherapy-free induction-consolidation protocol that combines dasatinib and blinatumomab for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) resulted in high survival and molecular response rates in the phase 2 D-ALBA trial.
At a median follow-up of 14.3 months, 61 of 63 patients enrolled in the multicenter trial had completed induction with the second-generation tyrosine kinase inhibitor (TKI) dasatinib, 60 had received the first cycle of treatment with the bispecific monoclonal antibody blinatumomab, and 56, 45, 36, and 25 had received second, third, fourth, and fifth cycles of blinatumomab, respectively, Sabina Chiaretti, MD, PhD, reported at the annual meeting of the American Society of Hematology.
The molecular response rate at the end of induction on day 85 was 29%, said Dr. Chiaretti of the department of translational and precision medicine, Sapienza University, Rome.
“Even more importantly, at the primary endpoint [the end of the second cycle of blinatumomab], 60% of patients were molecular responders,” she said.
Of note, the molecular response rate continued to increase with additional blinatumomab cycles; the rate was 79% after cycle 4, she said.
The overall survival (OS) and disease-free survival (DFS) rates also were “very exciting and promising” at 92.5% and 89.7%, respectively, she added.
DFS did not differ significantly based on molecular response at day 85 (100% vs. 87.4% in those with vs. without a molecular response; P = .154), but patients with p190 fusion protein had slightly worse DFS, compared with those who had p210 or both p190 and p210 fusion protein (83.5% vs. 100%; P = .48).
Study participants included adult Ph+ ALL patients with a median age of 54.5 years (range of 24.1-81.7 years) who were enrolled between May 2017 and January 2019; 54% were women and the median white blood cell count was 42 x109/L.
The percentage of study subjects with the p190, p210, and both p190/p210 fusion proteins was 65.1%, 27%, and 7.9% respectively, Dr. Chiaretti said.
Treatment included dasatinib at a dose of 140 mg/day as induction for 85 days along with steroids, which were started 7 days prior to induction and continued for a total of 31 days. Those who had a complete hematologic response (CHR) after induction received postinduction consolidation treatment with blinatumomab at a flat dose of 28 mcg/day for at least 2 cycles, and up to 3 additional cycles were allowed at physician discretion based on molecular response.
During the course of the study, 156 adverse events occurred, including 50 serious adverse events. The latter most often involved infections, including 6 cytomegalovirus infections and 6 cases of prolonged fever; one of those cases was likely related to blinatumomab.
Two patients died, including an 80-year-old woman who died during induction, and a patient who was in CHR. Six relapses occurred, including one that involved a major protocol violation; three were extramedullary.
Additional analyses in this study showed that the most frequent copy number aberration was, as expected based on the available literature, IKZF1 deletion, which was present in 25 of 46 available samples (54%). Of those, 11 (23.9%) were found to have the IKZF1-plus signature, defined as IKZF1 and/or PAX5 and/or CDKN2A/B deletions, she said.
Further, ABL1 mutational analysis conducted in 15 patients with evidence of MRD increase showed that 8 were wild type and 7 were mutated – with 6 of the 7 represented by the gatekeeper mutation T315I, and one by an E255K mutation. All but 1 mutation occurred in p190 cases prior to the start of blinatumomab.
Of note, and in line with prior findings, blinatumomab was effective for reducing or eradicating the MRD levels in these difficult-to-treat patients, Dr. Chiaretti said.
An analysis of the immunologic compartment carried out in 12 patients who completed all 5 cycles of blinatumomab showed a significant increase in the rate of CD8+ T cells (29% vs. 19.8% before the start of blinatumomab; P = .04) and a significant reduction in the rate of Tregs (3.7% vs. 11% before blinatumomab; P = .02), she added.
The findings of this study to date – with some patients having more than 2 years of follow-up – are notable given the high rates of molecular response and survival, Dr. Chiaretti said.
Outcomes in patients with Ph+ ALL were generally poor before the introduction of TKIs, but “the scenario completely changed,” she explained.
“In general, all TKI-based treatments – with or without chemotherapy – have led to overall survival rates in the range of 50% ... which means that we still need to improve our clinical management,” she said. “Another finding that became clear is the fact that patients who achieve MRD-negative status have a significantly better outcome than those who do not.”
The D-ALBA trial was designed with the aim of increasing the rate of MRD negativity in newly diagnosed patients using dasatinib and blinatumomab, and the results demonstrate that this chemotherapy-free induction/consolidation approach is feasible in the front-line setting for adult Ph+ ALL patients, she said, adding that “it is strongly effective in inducing high rates of MRD negativity, and it results in much better survival rates.”
The findings with respect to IKZF1-plus cases and ABL1 mutations underscore the need for further work, she said.
“We still have to face some challenging cases,” she explained. “This study, as others before, really proves that IKZF1-plus cases are very difficult to treat; they require intensification and probably alternative strategies.”
Dr. Chiaretti reported membership on a board of directors or advisory committee for Pfizer, Incyte, Amgen, and Shire.
SOURCE: Chiaretti S et al. ASH 2019, Abstract 740.
ORLANDO – A front-line chemotherapy-free induction-consolidation protocol that combines dasatinib and blinatumomab for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) resulted in high survival and molecular response rates in the phase 2 D-ALBA trial.
At a median follow-up of 14.3 months, 61 of 63 patients enrolled in the multicenter trial had completed induction with the second-generation tyrosine kinase inhibitor (TKI) dasatinib, 60 had received the first cycle of treatment with the bispecific monoclonal antibody blinatumomab, and 56, 45, 36, and 25 had received second, third, fourth, and fifth cycles of blinatumomab, respectively, Sabina Chiaretti, MD, PhD, reported at the annual meeting of the American Society of Hematology.
The molecular response rate at the end of induction on day 85 was 29%, said Dr. Chiaretti of the department of translational and precision medicine, Sapienza University, Rome.
“Even more importantly, at the primary endpoint [the end of the second cycle of blinatumomab], 60% of patients were molecular responders,” she said.
Of note, the molecular response rate continued to increase with additional blinatumomab cycles; the rate was 79% after cycle 4, she said.
The overall survival (OS) and disease-free survival (DFS) rates also were “very exciting and promising” at 92.5% and 89.7%, respectively, she added.
DFS did not differ significantly based on molecular response at day 85 (100% vs. 87.4% in those with vs. without a molecular response; P = .154), but patients with p190 fusion protein had slightly worse DFS, compared with those who had p210 or both p190 and p210 fusion protein (83.5% vs. 100%; P = .48).
Study participants included adult Ph+ ALL patients with a median age of 54.5 years (range of 24.1-81.7 years) who were enrolled between May 2017 and January 2019; 54% were women and the median white blood cell count was 42 x109/L.
The percentage of study subjects with the p190, p210, and both p190/p210 fusion proteins was 65.1%, 27%, and 7.9% respectively, Dr. Chiaretti said.
Treatment included dasatinib at a dose of 140 mg/day as induction for 85 days along with steroids, which were started 7 days prior to induction and continued for a total of 31 days. Those who had a complete hematologic response (CHR) after induction received postinduction consolidation treatment with blinatumomab at a flat dose of 28 mcg/day for at least 2 cycles, and up to 3 additional cycles were allowed at physician discretion based on molecular response.
During the course of the study, 156 adverse events occurred, including 50 serious adverse events. The latter most often involved infections, including 6 cytomegalovirus infections and 6 cases of prolonged fever; one of those cases was likely related to blinatumomab.
Two patients died, including an 80-year-old woman who died during induction, and a patient who was in CHR. Six relapses occurred, including one that involved a major protocol violation; three were extramedullary.
Additional analyses in this study showed that the most frequent copy number aberration was, as expected based on the available literature, IKZF1 deletion, which was present in 25 of 46 available samples (54%). Of those, 11 (23.9%) were found to have the IKZF1-plus signature, defined as IKZF1 and/or PAX5 and/or CDKN2A/B deletions, she said.
Further, ABL1 mutational analysis conducted in 15 patients with evidence of MRD increase showed that 8 were wild type and 7 were mutated – with 6 of the 7 represented by the gatekeeper mutation T315I, and one by an E255K mutation. All but 1 mutation occurred in p190 cases prior to the start of blinatumomab.
Of note, and in line with prior findings, blinatumomab was effective for reducing or eradicating the MRD levels in these difficult-to-treat patients, Dr. Chiaretti said.
An analysis of the immunologic compartment carried out in 12 patients who completed all 5 cycles of blinatumomab showed a significant increase in the rate of CD8+ T cells (29% vs. 19.8% before the start of blinatumomab; P = .04) and a significant reduction in the rate of Tregs (3.7% vs. 11% before blinatumomab; P = .02), she added.
The findings of this study to date – with some patients having more than 2 years of follow-up – are notable given the high rates of molecular response and survival, Dr. Chiaretti said.
Outcomes in patients with Ph+ ALL were generally poor before the introduction of TKIs, but “the scenario completely changed,” she explained.
“In general, all TKI-based treatments – with or without chemotherapy – have led to overall survival rates in the range of 50% ... which means that we still need to improve our clinical management,” she said. “Another finding that became clear is the fact that patients who achieve MRD-negative status have a significantly better outcome than those who do not.”
The D-ALBA trial was designed with the aim of increasing the rate of MRD negativity in newly diagnosed patients using dasatinib and blinatumomab, and the results demonstrate that this chemotherapy-free induction/consolidation approach is feasible in the front-line setting for adult Ph+ ALL patients, she said, adding that “it is strongly effective in inducing high rates of MRD negativity, and it results in much better survival rates.”
The findings with respect to IKZF1-plus cases and ABL1 mutations underscore the need for further work, she said.
“We still have to face some challenging cases,” she explained. “This study, as others before, really proves that IKZF1-plus cases are very difficult to treat; they require intensification and probably alternative strategies.”
Dr. Chiaretti reported membership on a board of directors or advisory committee for Pfizer, Incyte, Amgen, and Shire.
SOURCE: Chiaretti S et al. ASH 2019, Abstract 740.
ORLANDO – A front-line chemotherapy-free induction-consolidation protocol that combines dasatinib and blinatumomab for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) resulted in high survival and molecular response rates in the phase 2 D-ALBA trial.
At a median follow-up of 14.3 months, 61 of 63 patients enrolled in the multicenter trial had completed induction with the second-generation tyrosine kinase inhibitor (TKI) dasatinib, 60 had received the first cycle of treatment with the bispecific monoclonal antibody blinatumomab, and 56, 45, 36, and 25 had received second, third, fourth, and fifth cycles of blinatumomab, respectively, Sabina Chiaretti, MD, PhD, reported at the annual meeting of the American Society of Hematology.
The molecular response rate at the end of induction on day 85 was 29%, said Dr. Chiaretti of the department of translational and precision medicine, Sapienza University, Rome.
“Even more importantly, at the primary endpoint [the end of the second cycle of blinatumomab], 60% of patients were molecular responders,” she said.
Of note, the molecular response rate continued to increase with additional blinatumomab cycles; the rate was 79% after cycle 4, she said.
The overall survival (OS) and disease-free survival (DFS) rates also were “very exciting and promising” at 92.5% and 89.7%, respectively, she added.
DFS did not differ significantly based on molecular response at day 85 (100% vs. 87.4% in those with vs. without a molecular response; P = .154), but patients with p190 fusion protein had slightly worse DFS, compared with those who had p210 or both p190 and p210 fusion protein (83.5% vs. 100%; P = .48).
Study participants included adult Ph+ ALL patients with a median age of 54.5 years (range of 24.1-81.7 years) who were enrolled between May 2017 and January 2019; 54% were women and the median white blood cell count was 42 x109/L.
The percentage of study subjects with the p190, p210, and both p190/p210 fusion proteins was 65.1%, 27%, and 7.9% respectively, Dr. Chiaretti said.
Treatment included dasatinib at a dose of 140 mg/day as induction for 85 days along with steroids, which were started 7 days prior to induction and continued for a total of 31 days. Those who had a complete hematologic response (CHR) after induction received postinduction consolidation treatment with blinatumomab at a flat dose of 28 mcg/day for at least 2 cycles, and up to 3 additional cycles were allowed at physician discretion based on molecular response.
During the course of the study, 156 adverse events occurred, including 50 serious adverse events. The latter most often involved infections, including 6 cytomegalovirus infections and 6 cases of prolonged fever; one of those cases was likely related to blinatumomab.
Two patients died, including an 80-year-old woman who died during induction, and a patient who was in CHR. Six relapses occurred, including one that involved a major protocol violation; three were extramedullary.
Additional analyses in this study showed that the most frequent copy number aberration was, as expected based on the available literature, IKZF1 deletion, which was present in 25 of 46 available samples (54%). Of those, 11 (23.9%) were found to have the IKZF1-plus signature, defined as IKZF1 and/or PAX5 and/or CDKN2A/B deletions, she said.
Further, ABL1 mutational analysis conducted in 15 patients with evidence of MRD increase showed that 8 were wild type and 7 were mutated – with 6 of the 7 represented by the gatekeeper mutation T315I, and one by an E255K mutation. All but 1 mutation occurred in p190 cases prior to the start of blinatumomab.
Of note, and in line with prior findings, blinatumomab was effective for reducing or eradicating the MRD levels in these difficult-to-treat patients, Dr. Chiaretti said.
An analysis of the immunologic compartment carried out in 12 patients who completed all 5 cycles of blinatumomab showed a significant increase in the rate of CD8+ T cells (29% vs. 19.8% before the start of blinatumomab; P = .04) and a significant reduction in the rate of Tregs (3.7% vs. 11% before blinatumomab; P = .02), she added.
The findings of this study to date – with some patients having more than 2 years of follow-up – are notable given the high rates of molecular response and survival, Dr. Chiaretti said.
Outcomes in patients with Ph+ ALL were generally poor before the introduction of TKIs, but “the scenario completely changed,” she explained.
“In general, all TKI-based treatments – with or without chemotherapy – have led to overall survival rates in the range of 50% ... which means that we still need to improve our clinical management,” she said. “Another finding that became clear is the fact that patients who achieve MRD-negative status have a significantly better outcome than those who do not.”
The D-ALBA trial was designed with the aim of increasing the rate of MRD negativity in newly diagnosed patients using dasatinib and blinatumomab, and the results demonstrate that this chemotherapy-free induction/consolidation approach is feasible in the front-line setting for adult Ph+ ALL patients, she said, adding that “it is strongly effective in inducing high rates of MRD negativity, and it results in much better survival rates.”
The findings with respect to IKZF1-plus cases and ABL1 mutations underscore the need for further work, she said.
“We still have to face some challenging cases,” she explained. “This study, as others before, really proves that IKZF1-plus cases are very difficult to treat; they require intensification and probably alternative strategies.”
Dr. Chiaretti reported membership on a board of directors or advisory committee for Pfizer, Incyte, Amgen, and Shire.
SOURCE: Chiaretti S et al. ASH 2019, Abstract 740.
REPORTING FROM ASH 2019
COACT: No benefit of immediate PCI for non–ST-elevation cardiac arrest at 1 year
PHILADELPHIA – Immediate coronary angiography following restoration of spontaneous circulation after out-of-hospital cardiac arrest without ST-elevation MI (STEMI) offered no survival benefit at 1 year, compared with a strategy of delaying angiography until after neurologic recovery, in the landmark COACT trial, Jorrit Lemkes, MD, reported at the American Heart Association scientific sessions.
Nor was immediate coronary angiography advantageous in terms of any of the numerous secondary long-term endpoints, including rates of MI, revascularization, hospitalization for heart failure, implantable cardioverter defibrillator (ICD) shocks, or quality of life measures (see graphic), according to Dr. Lemkes, an interventional cardiologist at Amsterdam University Medical Center.
COACT, a 552-patient randomized trial conducted at 19 Dutch centers, was the first-ever randomized trial to evaluate the role of immediate coronary angiography in patients resuscitated from out-of-hospital cardiac arrest with no signs of ST elevation on ECG. The study hypothesis was that this practice would result in improved survival and other outcomes. But such was not the case in the previously reported 90-day analysis (N Engl J Med. 2019 Apr 11;380[15]:1397-407). Nonetheless, the new 1-year results were eagerly awaited because observational data had suggested that immediate angiography after cardiac arrest without STEMI might provide a survival advantage that manifests late.
It now appears the observational studies were misleading. The 1-year survival rate was 61.4% in the immediate angioplasty group and similar at 64% with delayed angioplasty.
By way of background, Dr. Lemkes noted that both European and American guidelines give a class 1 recommendation to immediate coronary angiography with percutaneous coronary intervention (PCI) in patients who present with STEMI and cardiac arrest. It’s an endorsement grounded in compelling clinical trials evidence demonstrating that this practice reduces mortality and recurrent ischemia, salvages myocardium, and restores left ventricular function. In contrast, current guidelines offer only a tepid recommendation for immediate PCI in patients with cardiac arrest without STEMI because the only supporting evidence has been observational, with its inherent susceptibility to bias.
Discussant Joaquin E. Cigarroa, MD, said that the 1-year outcomes shouldn’t be surprising, since the 90-day results failed to show any between-group differences in myocardial injury or ischemia.
“At present, the results of COACT with regards to primary and secondary outcomes should guide practitioners that angiography remains essential, but that early angiography does not improve outcomes, compared to delayed angiography,” declared Dr. Cigarroa, chief of cardiology and professor of medicine at Oregon Health & Science University, Portland.
His choice of the words “at present” was key, as COACT won’t be the last word on the subject. Dr. Cigarroa believes that it’s critically important to understand the relatively narrow profile of the patients included in the study, because the results may or may not prove to be generalizable to the broader population of out-of-hospital cardiac arrest patients encountered in clinical practice. Nearly 80% of COACT participants had a witnessed arrest, the median time to basic life support was just 2 minutes, and the median time to return of spontaneous circulation was 15 minutes.
He urged his colleagues to stay tuned for reports from ongoing randomized trials examining the potential role of immediate angiography in broader populations of patients with out-of-hospital cardiac arrest without STEMI, including the Swedish DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial and the smaller University of Minnesota–sponsored ACCESS trial.
Dr. Lemkes reported having no financial conflicts regarding the COACT trial, funded by the Netherlands Heart Institute and unrestricted research grants from Biotronik and AstraZeneca.
PHILADELPHIA – Immediate coronary angiography following restoration of spontaneous circulation after out-of-hospital cardiac arrest without ST-elevation MI (STEMI) offered no survival benefit at 1 year, compared with a strategy of delaying angiography until after neurologic recovery, in the landmark COACT trial, Jorrit Lemkes, MD, reported at the American Heart Association scientific sessions.
Nor was immediate coronary angiography advantageous in terms of any of the numerous secondary long-term endpoints, including rates of MI, revascularization, hospitalization for heart failure, implantable cardioverter defibrillator (ICD) shocks, or quality of life measures (see graphic), according to Dr. Lemkes, an interventional cardiologist at Amsterdam University Medical Center.
COACT, a 552-patient randomized trial conducted at 19 Dutch centers, was the first-ever randomized trial to evaluate the role of immediate coronary angiography in patients resuscitated from out-of-hospital cardiac arrest with no signs of ST elevation on ECG. The study hypothesis was that this practice would result in improved survival and other outcomes. But such was not the case in the previously reported 90-day analysis (N Engl J Med. 2019 Apr 11;380[15]:1397-407). Nonetheless, the new 1-year results were eagerly awaited because observational data had suggested that immediate angiography after cardiac arrest without STEMI might provide a survival advantage that manifests late.
It now appears the observational studies were misleading. The 1-year survival rate was 61.4% in the immediate angioplasty group and similar at 64% with delayed angioplasty.
By way of background, Dr. Lemkes noted that both European and American guidelines give a class 1 recommendation to immediate coronary angiography with percutaneous coronary intervention (PCI) in patients who present with STEMI and cardiac arrest. It’s an endorsement grounded in compelling clinical trials evidence demonstrating that this practice reduces mortality and recurrent ischemia, salvages myocardium, and restores left ventricular function. In contrast, current guidelines offer only a tepid recommendation for immediate PCI in patients with cardiac arrest without STEMI because the only supporting evidence has been observational, with its inherent susceptibility to bias.
Discussant Joaquin E. Cigarroa, MD, said that the 1-year outcomes shouldn’t be surprising, since the 90-day results failed to show any between-group differences in myocardial injury or ischemia.
“At present, the results of COACT with regards to primary and secondary outcomes should guide practitioners that angiography remains essential, but that early angiography does not improve outcomes, compared to delayed angiography,” declared Dr. Cigarroa, chief of cardiology and professor of medicine at Oregon Health & Science University, Portland.
His choice of the words “at present” was key, as COACT won’t be the last word on the subject. Dr. Cigarroa believes that it’s critically important to understand the relatively narrow profile of the patients included in the study, because the results may or may not prove to be generalizable to the broader population of out-of-hospital cardiac arrest patients encountered in clinical practice. Nearly 80% of COACT participants had a witnessed arrest, the median time to basic life support was just 2 minutes, and the median time to return of spontaneous circulation was 15 minutes.
He urged his colleagues to stay tuned for reports from ongoing randomized trials examining the potential role of immediate angiography in broader populations of patients with out-of-hospital cardiac arrest without STEMI, including the Swedish DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial and the smaller University of Minnesota–sponsored ACCESS trial.
Dr. Lemkes reported having no financial conflicts regarding the COACT trial, funded by the Netherlands Heart Institute and unrestricted research grants from Biotronik and AstraZeneca.
PHILADELPHIA – Immediate coronary angiography following restoration of spontaneous circulation after out-of-hospital cardiac arrest without ST-elevation MI (STEMI) offered no survival benefit at 1 year, compared with a strategy of delaying angiography until after neurologic recovery, in the landmark COACT trial, Jorrit Lemkes, MD, reported at the American Heart Association scientific sessions.
Nor was immediate coronary angiography advantageous in terms of any of the numerous secondary long-term endpoints, including rates of MI, revascularization, hospitalization for heart failure, implantable cardioverter defibrillator (ICD) shocks, or quality of life measures (see graphic), according to Dr. Lemkes, an interventional cardiologist at Amsterdam University Medical Center.
COACT, a 552-patient randomized trial conducted at 19 Dutch centers, was the first-ever randomized trial to evaluate the role of immediate coronary angiography in patients resuscitated from out-of-hospital cardiac arrest with no signs of ST elevation on ECG. The study hypothesis was that this practice would result in improved survival and other outcomes. But such was not the case in the previously reported 90-day analysis (N Engl J Med. 2019 Apr 11;380[15]:1397-407). Nonetheless, the new 1-year results were eagerly awaited because observational data had suggested that immediate angiography after cardiac arrest without STEMI might provide a survival advantage that manifests late.
It now appears the observational studies were misleading. The 1-year survival rate was 61.4% in the immediate angioplasty group and similar at 64% with delayed angioplasty.
By way of background, Dr. Lemkes noted that both European and American guidelines give a class 1 recommendation to immediate coronary angiography with percutaneous coronary intervention (PCI) in patients who present with STEMI and cardiac arrest. It’s an endorsement grounded in compelling clinical trials evidence demonstrating that this practice reduces mortality and recurrent ischemia, salvages myocardium, and restores left ventricular function. In contrast, current guidelines offer only a tepid recommendation for immediate PCI in patients with cardiac arrest without STEMI because the only supporting evidence has been observational, with its inherent susceptibility to bias.
Discussant Joaquin E. Cigarroa, MD, said that the 1-year outcomes shouldn’t be surprising, since the 90-day results failed to show any between-group differences in myocardial injury or ischemia.
“At present, the results of COACT with regards to primary and secondary outcomes should guide practitioners that angiography remains essential, but that early angiography does not improve outcomes, compared to delayed angiography,” declared Dr. Cigarroa, chief of cardiology and professor of medicine at Oregon Health & Science University, Portland.
His choice of the words “at present” was key, as COACT won’t be the last word on the subject. Dr. Cigarroa believes that it’s critically important to understand the relatively narrow profile of the patients included in the study, because the results may or may not prove to be generalizable to the broader population of out-of-hospital cardiac arrest patients encountered in clinical practice. Nearly 80% of COACT participants had a witnessed arrest, the median time to basic life support was just 2 minutes, and the median time to return of spontaneous circulation was 15 minutes.
He urged his colleagues to stay tuned for reports from ongoing randomized trials examining the potential role of immediate angiography in broader populations of patients with out-of-hospital cardiac arrest without STEMI, including the Swedish DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial and the smaller University of Minnesota–sponsored ACCESS trial.
Dr. Lemkes reported having no financial conflicts regarding the COACT trial, funded by the Netherlands Heart Institute and unrestricted research grants from Biotronik and AstraZeneca.
REPORTING FROM AHA 2019
State of Practice: Unresectable Stage III NSCLC
In this issue of CHEST Clinical Perspectives, CHEST is undertaking primary research with pulmonologists to assess perceptions regarding curative intent when it comes to treating patients diagnosed with stage III NSCLC. The objectives of this research are to:
- Understand the role of the pulmonologist in diagnostic process, including diagnosis, cell type, staging.
- Understand the process of referral for treatment of patients with stage III NSCLC diagnosed in pulmonary practices, including frequency of referral to oncology and barriers to referral.
- Understand knowledge levels about stage III NSCLC, including differences between patients with stage III and stage IV and how that impacts referral for treatment.
- Understand the extent to which pulmonologists consider stage III patients to be in a curative state.
In this issue of CHEST Clinical Perspectives, CHEST is undertaking primary research with pulmonologists to assess perceptions regarding curative intent when it comes to treating patients diagnosed with stage III NSCLC. The objectives of this research are to:
- Understand the role of the pulmonologist in diagnostic process, including diagnosis, cell type, staging.
- Understand the process of referral for treatment of patients with stage III NSCLC diagnosed in pulmonary practices, including frequency of referral to oncology and barriers to referral.
- Understand knowledge levels about stage III NSCLC, including differences between patients with stage III and stage IV and how that impacts referral for treatment.
- Understand the extent to which pulmonologists consider stage III patients to be in a curative state.
In this issue of CHEST Clinical Perspectives, CHEST is undertaking primary research with pulmonologists to assess perceptions regarding curative intent when it comes to treating patients diagnosed with stage III NSCLC. The objectives of this research are to:
- Understand the role of the pulmonologist in diagnostic process, including diagnosis, cell type, staging.
- Understand the process of referral for treatment of patients with stage III NSCLC diagnosed in pulmonary practices, including frequency of referral to oncology and barriers to referral.
- Understand knowledge levels about stage III NSCLC, including differences between patients with stage III and stage IV and how that impacts referral for treatment.
- Understand the extent to which pulmonologists consider stage III patients to be in a curative state.