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Developments in gastric cancer
In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).
Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.
GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).
Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.
On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.
On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.
In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).
Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.
GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).
Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.
On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.
On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.
In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).
Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.
GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).
Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.
On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.
On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.
Upper and lower gastroenterology – the state of the art
In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.
In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.
In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.
In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.
In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.
In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.
Large prospective trial offers reassurance for long-term PPI use
Aside from a possible increased risk of enteric infections, long-term use of the proton pump inhibitor (PPI) pantoprazole appears safe in patients with stable atherosclerotic vascular disease, according to a prospective trial involving more than 17,000 participants.
In contrast with published observational studies, the present trial found no associations between long-term PPI use and previously reported risks such as pneumonia, fracture, or cerebrovascular events, according to lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Ont., and colleagues.
“To our knowledge, this is the largest PPI trial for any indication and the first prospective randomized trial to evaluate the many long-term safety concerns related to PPI therapy,” the investigators wrote in Gastroenterology. “It is reassuring that there was no evidence for harm for most of these events other than an excess of enteric infections.”
“Given how commonly acid suppressive medications are used, it is important to ensure that this class of drugs is safe,” the investigators wrote. They noted that patients are often alarmed by “sensational headlines” about PPI safety. “There are balancing articles that more carefully discuss the risks and benefits of taking PPI therapy but these receive less media attention,” the investigators added.
The present, prospective trial, COMPASS, involved 17,598 participants from 33 countries with stable peripheral artery disease and cardiovascular disease. “We use the term participants, rather than patients, as not all of those taking part in this research would have been patients throughout the trial but all participated in the randomized controlled trial,” the investigators wrote.
In addition to evaluating the safety of pantoprazole, the study was initially designed to measure the efficacy of pantoprazole for preventing upper gastrointestinal events in participants taking rivaroxaban and/or aspirin, which, in combination, were recently shown to reduce cardiovascular outcomes among patients with stable cardiovascular conditions. As such, participants in the trial were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or 2.5-mg rivaroxaban twice daily combined with 100-mg aspirin once daily. The primary efficacy outcomes for these three groups were stroke, myocardial infarction, and cardiovascular death. This portion of the trial was discontinued early because of evidence that showed the superiority of combination therapy over aspirin alone; however, the pantoprazole component of the trial continued, as planned, for 3 years.
At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. Pantoprazole safety outcomes centered on those previously reported by observational studies, including dementia, chronic kidney disease, gastric atrophy, fracture, cancer, pneumonia, diabetes mellitus, chronic obstructive lung disease, Clostrididoides difficile infection, and other enteric infections. Hospitalization rates for noncardiovascular and cardiovascular events were also reported. Data were gathered via questionnaires, which were conducted every 6 months.
Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking an NSAID (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.
Analysis of cardiovascular outcomes revealed no significant differences between placebo and pantoprazole groups. Of all the evaluated safety measures, only enteric infections differed significantly between groups, occurring at a higher rate in the pantoprazole group than in the placebo group (1.4% vs. 1.0%; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). Although C. difficile infection was more common among pantoprazole users, only 13 such events occurred, precluding statistical significance.
According to the investigators, these findings should offer reassurance to PPI prescribers and users; they noted that previous findings from observational studies warrant skepticism. “A significant proportion of patients are prescribed PPI therapy inappropriately, and in these cases, it is reasonable to advocate strategies to discontinue acid suppression. However, when there is a clinical need for PPI therapy, these data suggest that the benefits are likely to outweigh any putative risks.”
In regard to the possible increased risk of enteric infection, the investigators again urged a conservative interpretation, as the increased rate of enteric infection among PPI users was still lower than rates reported by systematic reviews. “The data in the current randomized trial were not adjusted for multiple testing so this result should be interpreted with caution,” the investigators wrote. Although acid suppression may allow for increased ingestion of pathogenic organisms, which could theoretically increase the risk of enteric infection, the investigators stated that the benefits of PPIs likely outweigh their risks.
The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Bayer, Allergan, Takeda, Janssen, and others.
SOURCE: Moayyedi P et al. Gastro. 2019 May 29. doi: 10.1053/j.gastro.2019.05.056.
AGA patient education on GERD can help your patients better understand and manage the disorder. Post this education or your practice website or share you’re your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.
Aside from a possible increased risk of enteric infections, long-term use of the proton pump inhibitor (PPI) pantoprazole appears safe in patients with stable atherosclerotic vascular disease, according to a prospective trial involving more than 17,000 participants.
In contrast with published observational studies, the present trial found no associations between long-term PPI use and previously reported risks such as pneumonia, fracture, or cerebrovascular events, according to lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Ont., and colleagues.
“To our knowledge, this is the largest PPI trial for any indication and the first prospective randomized trial to evaluate the many long-term safety concerns related to PPI therapy,” the investigators wrote in Gastroenterology. “It is reassuring that there was no evidence for harm for most of these events other than an excess of enteric infections.”
“Given how commonly acid suppressive medications are used, it is important to ensure that this class of drugs is safe,” the investigators wrote. They noted that patients are often alarmed by “sensational headlines” about PPI safety. “There are balancing articles that more carefully discuss the risks and benefits of taking PPI therapy but these receive less media attention,” the investigators added.
The present, prospective trial, COMPASS, involved 17,598 participants from 33 countries with stable peripheral artery disease and cardiovascular disease. “We use the term participants, rather than patients, as not all of those taking part in this research would have been patients throughout the trial but all participated in the randomized controlled trial,” the investigators wrote.
In addition to evaluating the safety of pantoprazole, the study was initially designed to measure the efficacy of pantoprazole for preventing upper gastrointestinal events in participants taking rivaroxaban and/or aspirin, which, in combination, were recently shown to reduce cardiovascular outcomes among patients with stable cardiovascular conditions. As such, participants in the trial were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or 2.5-mg rivaroxaban twice daily combined with 100-mg aspirin once daily. The primary efficacy outcomes for these three groups were stroke, myocardial infarction, and cardiovascular death. This portion of the trial was discontinued early because of evidence that showed the superiority of combination therapy over aspirin alone; however, the pantoprazole component of the trial continued, as planned, for 3 years.
At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. Pantoprazole safety outcomes centered on those previously reported by observational studies, including dementia, chronic kidney disease, gastric atrophy, fracture, cancer, pneumonia, diabetes mellitus, chronic obstructive lung disease, Clostrididoides difficile infection, and other enteric infections. Hospitalization rates for noncardiovascular and cardiovascular events were also reported. Data were gathered via questionnaires, which were conducted every 6 months.
Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking an NSAID (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.
Analysis of cardiovascular outcomes revealed no significant differences between placebo and pantoprazole groups. Of all the evaluated safety measures, only enteric infections differed significantly between groups, occurring at a higher rate in the pantoprazole group than in the placebo group (1.4% vs. 1.0%; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). Although C. difficile infection was more common among pantoprazole users, only 13 such events occurred, precluding statistical significance.
According to the investigators, these findings should offer reassurance to PPI prescribers and users; they noted that previous findings from observational studies warrant skepticism. “A significant proportion of patients are prescribed PPI therapy inappropriately, and in these cases, it is reasonable to advocate strategies to discontinue acid suppression. However, when there is a clinical need for PPI therapy, these data suggest that the benefits are likely to outweigh any putative risks.”
In regard to the possible increased risk of enteric infection, the investigators again urged a conservative interpretation, as the increased rate of enteric infection among PPI users was still lower than rates reported by systematic reviews. “The data in the current randomized trial were not adjusted for multiple testing so this result should be interpreted with caution,” the investigators wrote. Although acid suppression may allow for increased ingestion of pathogenic organisms, which could theoretically increase the risk of enteric infection, the investigators stated that the benefits of PPIs likely outweigh their risks.
The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Bayer, Allergan, Takeda, Janssen, and others.
SOURCE: Moayyedi P et al. Gastro. 2019 May 29. doi: 10.1053/j.gastro.2019.05.056.
AGA patient education on GERD can help your patients better understand and manage the disorder. Post this education or your practice website or share you’re your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.
Aside from a possible increased risk of enteric infections, long-term use of the proton pump inhibitor (PPI) pantoprazole appears safe in patients with stable atherosclerotic vascular disease, according to a prospective trial involving more than 17,000 participants.
In contrast with published observational studies, the present trial found no associations between long-term PPI use and previously reported risks such as pneumonia, fracture, or cerebrovascular events, according to lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Ont., and colleagues.
“To our knowledge, this is the largest PPI trial for any indication and the first prospective randomized trial to evaluate the many long-term safety concerns related to PPI therapy,” the investigators wrote in Gastroenterology. “It is reassuring that there was no evidence for harm for most of these events other than an excess of enteric infections.”
“Given how commonly acid suppressive medications are used, it is important to ensure that this class of drugs is safe,” the investigators wrote. They noted that patients are often alarmed by “sensational headlines” about PPI safety. “There are balancing articles that more carefully discuss the risks and benefits of taking PPI therapy but these receive less media attention,” the investigators added.
The present, prospective trial, COMPASS, involved 17,598 participants from 33 countries with stable peripheral artery disease and cardiovascular disease. “We use the term participants, rather than patients, as not all of those taking part in this research would have been patients throughout the trial but all participated in the randomized controlled trial,” the investigators wrote.
In addition to evaluating the safety of pantoprazole, the study was initially designed to measure the efficacy of pantoprazole for preventing upper gastrointestinal events in participants taking rivaroxaban and/or aspirin, which, in combination, were recently shown to reduce cardiovascular outcomes among patients with stable cardiovascular conditions. As such, participants in the trial were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or 2.5-mg rivaroxaban twice daily combined with 100-mg aspirin once daily. The primary efficacy outcomes for these three groups were stroke, myocardial infarction, and cardiovascular death. This portion of the trial was discontinued early because of evidence that showed the superiority of combination therapy over aspirin alone; however, the pantoprazole component of the trial continued, as planned, for 3 years.
At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. Pantoprazole safety outcomes centered on those previously reported by observational studies, including dementia, chronic kidney disease, gastric atrophy, fracture, cancer, pneumonia, diabetes mellitus, chronic obstructive lung disease, Clostrididoides difficile infection, and other enteric infections. Hospitalization rates for noncardiovascular and cardiovascular events were also reported. Data were gathered via questionnaires, which were conducted every 6 months.
Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking an NSAID (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.
Analysis of cardiovascular outcomes revealed no significant differences between placebo and pantoprazole groups. Of all the evaluated safety measures, only enteric infections differed significantly between groups, occurring at a higher rate in the pantoprazole group than in the placebo group (1.4% vs. 1.0%; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). Although C. difficile infection was more common among pantoprazole users, only 13 such events occurred, precluding statistical significance.
According to the investigators, these findings should offer reassurance to PPI prescribers and users; they noted that previous findings from observational studies warrant skepticism. “A significant proportion of patients are prescribed PPI therapy inappropriately, and in these cases, it is reasonable to advocate strategies to discontinue acid suppression. However, when there is a clinical need for PPI therapy, these data suggest that the benefits are likely to outweigh any putative risks.”
In regard to the possible increased risk of enteric infection, the investigators again urged a conservative interpretation, as the increased rate of enteric infection among PPI users was still lower than rates reported by systematic reviews. “The data in the current randomized trial were not adjusted for multiple testing so this result should be interpreted with caution,” the investigators wrote. Although acid suppression may allow for increased ingestion of pathogenic organisms, which could theoretically increase the risk of enteric infection, the investigators stated that the benefits of PPIs likely outweigh their risks.
The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Bayer, Allergan, Takeda, Janssen, and others.
SOURCE: Moayyedi P et al. Gastro. 2019 May 29. doi: 10.1053/j.gastro.2019.05.056.
AGA patient education on GERD can help your patients better understand and manage the disorder. Post this education or your practice website or share you’re your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.
FROM GASTROENTEROLOGY
Key clinical point: Aside from a possible increased risk of enteric infections, long-term use of pantoprazole is safe in patients with stable peripheral artery and cardiovascular disease.
Major finding: Enteric infections were 33% more common in the pantoprazole group than in the placebo group.
Study details: A placebo-controlled, double-blind, randomized trial involving 17,598 patients with stable peripheral artery disease and cardiovascular disease.
Disclosures: The COMPASS trial was funded by Bayer AG. The investigators disclosed relationships with Bayer, Allergan, Takeda, Janssen, and others.
Source: Moayyedi P et al. Gastroenterology. 2019 May 29. doi: 10.1053/j.gastro.2019.05.056.
Pantoprazole not needed for most patients on anticoagulant/antiplatelet therapies
For most patients taking antiplatelet and/or anticoagulant therapies, the proton pump inhibitor (PPI) pantoprazole is unnecessary, based on findings from the prospective COMPASS trial, which involved more than 17,000 participants.
Pantoprazole may reduce the risk of bleeding from gastroduodenal lesions, but it is unlikely to prevent upper-gastrointestinal events, reported lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Canada, and colleagues.
The investigators wrote in Gastroenterology, “Guidelines suggest that patients receiving the combination of antiplatelet and anticoagulant therapy should receive PPIs to reduce the risk of upper-GI bleeding. However … there are no randomized data to support the use of PPI therapy in patients taking oral anticoagulants, and a paucity of data relating to aspirin.”
To fill this knowledge gap, the investigators recruited 17,598 participants from 33 countries who had stable peripheral artery disease and cardiovascular disease. Participants were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or a combination of 2.5-mg rivaroxaban twice daily with 100-mg aspirin once daily. This part of the trial was discontinued before completion because of early cardiovascular advantages associated with combination therapy over aspirin alone, and related findings were reported previously. While combination therapy did reduce cardiovascular risks, it had less favorable effects on gut health, highlighted by an associated increase in major GI bleeding events. Despite early cessation of the cardiovascular portion of the trial, the pantoprazole regimen was continued, offering a look at the effect of long-term PPI use on gut health.
At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. The primary efficacy outcome was time to first upper-GI clinical event, defined as a composite of the following: upper-GI obstruction, perforation, at least five gastroduodenal erosions with at least 3 days of GI pain, symptomatic gastroduodenal ulcer involving at least 3 days of GI pain, overt upper-GI bleeding of unknown origin, occult bleeding (drop in hemoglobin of at least 2 g/dL), overt bleeding with a gastroduodenal lesion (active bleeding during endoscopy), or a symptomatic gastroduodenal ulcer involving at least 3 days of GI pain. In addition to this measure, the investigators evaluated a post-hoc endpoint with a looser definition of peptic ulcer events, most notably eliminating the requirement that a lesion be actively bleeding during endoscopy.
Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking a nonsteroidal anti-inflammatory drug (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group, after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.
Analysis showed that upper-GI events occurred marginally less often in the pantoprazole group than the placebo group, but without statistical significance (1.2% vs. 1.3%; P = .35). Of the outcomes measured, only overt bleeding of gastroduodenal origin detected by radiography or endoscopy was statistically less common in the pantoprazole group than the placebo group, with a 48% reduced rate (0.2% vs. 0.4%; P = .03). No statistical efficacy differences or statistical interactions were detected between population subgroups.
“The data suggest that routine use of PPI therapy is not warranted for patients receiving low-dose rivaroxaban with or without aspirin for the prevention of atherothrombotic events in patients with stable coronary artery disease or symptomatic peripheral artery disease, as there was no overall impact on clinical upper-GI events or upper-GI bleeding,” the investigators wrote. “This is in contrast to previous systematic reviews of randomized trials reporting that PPIs were associated with a 50%-70% reduction in bleeding and symptomatic peptic ulcers related to nonsteroidal anti-inflammatory drugs, including in the critical care setting.”
Post-hoc analysis, which allowed for a broader definition of upper-GI events related to gastroduodenal ulcers, revealed a slightly greater reduction in risk of bleeding lesions in patients taking pantoprazole, compared with placebo (hazard ratio, 0.45), and additional risk reductions for peptic ulcers (HR, 0.46) and erosions (HR, 0.33). Ultimately, pantoprazole reduced the combined rate of post-hoc events by 56%.
The investigators noted that these ulcer- and erosion-reducing effects of pantoprazole align with previous reports. “It is therefore possible that PPIs might be beneficial for patients at particularly high risk for peptic ulcer disease who are also taking aspirin and/or anticoagulants,” the investigators concluded.
The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Allergan, Takeda, Janssen, and others.
SOURCE: Moayyedi P et al. Gastro. 2019 May 2. doi: 10.1053/j.gastro.2019.04.041.
For most patients taking antiplatelet and/or anticoagulant therapies, the proton pump inhibitor (PPI) pantoprazole is unnecessary, based on findings from the prospective COMPASS trial, which involved more than 17,000 participants.
Pantoprazole may reduce the risk of bleeding from gastroduodenal lesions, but it is unlikely to prevent upper-gastrointestinal events, reported lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Canada, and colleagues.
The investigators wrote in Gastroenterology, “Guidelines suggest that patients receiving the combination of antiplatelet and anticoagulant therapy should receive PPIs to reduce the risk of upper-GI bleeding. However … there are no randomized data to support the use of PPI therapy in patients taking oral anticoagulants, and a paucity of data relating to aspirin.”
To fill this knowledge gap, the investigators recruited 17,598 participants from 33 countries who had stable peripheral artery disease and cardiovascular disease. Participants were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or a combination of 2.5-mg rivaroxaban twice daily with 100-mg aspirin once daily. This part of the trial was discontinued before completion because of early cardiovascular advantages associated with combination therapy over aspirin alone, and related findings were reported previously. While combination therapy did reduce cardiovascular risks, it had less favorable effects on gut health, highlighted by an associated increase in major GI bleeding events. Despite early cessation of the cardiovascular portion of the trial, the pantoprazole regimen was continued, offering a look at the effect of long-term PPI use on gut health.
At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. The primary efficacy outcome was time to first upper-GI clinical event, defined as a composite of the following: upper-GI obstruction, perforation, at least five gastroduodenal erosions with at least 3 days of GI pain, symptomatic gastroduodenal ulcer involving at least 3 days of GI pain, overt upper-GI bleeding of unknown origin, occult bleeding (drop in hemoglobin of at least 2 g/dL), overt bleeding with a gastroduodenal lesion (active bleeding during endoscopy), or a symptomatic gastroduodenal ulcer involving at least 3 days of GI pain. In addition to this measure, the investigators evaluated a post-hoc endpoint with a looser definition of peptic ulcer events, most notably eliminating the requirement that a lesion be actively bleeding during endoscopy.
Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking a nonsteroidal anti-inflammatory drug (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group, after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.
Analysis showed that upper-GI events occurred marginally less often in the pantoprazole group than the placebo group, but without statistical significance (1.2% vs. 1.3%; P = .35). Of the outcomes measured, only overt bleeding of gastroduodenal origin detected by radiography or endoscopy was statistically less common in the pantoprazole group than the placebo group, with a 48% reduced rate (0.2% vs. 0.4%; P = .03). No statistical efficacy differences or statistical interactions were detected between population subgroups.
“The data suggest that routine use of PPI therapy is not warranted for patients receiving low-dose rivaroxaban with or without aspirin for the prevention of atherothrombotic events in patients with stable coronary artery disease or symptomatic peripheral artery disease, as there was no overall impact on clinical upper-GI events or upper-GI bleeding,” the investigators wrote. “This is in contrast to previous systematic reviews of randomized trials reporting that PPIs were associated with a 50%-70% reduction in bleeding and symptomatic peptic ulcers related to nonsteroidal anti-inflammatory drugs, including in the critical care setting.”
Post-hoc analysis, which allowed for a broader definition of upper-GI events related to gastroduodenal ulcers, revealed a slightly greater reduction in risk of bleeding lesions in patients taking pantoprazole, compared with placebo (hazard ratio, 0.45), and additional risk reductions for peptic ulcers (HR, 0.46) and erosions (HR, 0.33). Ultimately, pantoprazole reduced the combined rate of post-hoc events by 56%.
The investigators noted that these ulcer- and erosion-reducing effects of pantoprazole align with previous reports. “It is therefore possible that PPIs might be beneficial for patients at particularly high risk for peptic ulcer disease who are also taking aspirin and/or anticoagulants,” the investigators concluded.
The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Allergan, Takeda, Janssen, and others.
SOURCE: Moayyedi P et al. Gastro. 2019 May 2. doi: 10.1053/j.gastro.2019.04.041.
For most patients taking antiplatelet and/or anticoagulant therapies, the proton pump inhibitor (PPI) pantoprazole is unnecessary, based on findings from the prospective COMPASS trial, which involved more than 17,000 participants.
Pantoprazole may reduce the risk of bleeding from gastroduodenal lesions, but it is unlikely to prevent upper-gastrointestinal events, reported lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Canada, and colleagues.
The investigators wrote in Gastroenterology, “Guidelines suggest that patients receiving the combination of antiplatelet and anticoagulant therapy should receive PPIs to reduce the risk of upper-GI bleeding. However … there are no randomized data to support the use of PPI therapy in patients taking oral anticoagulants, and a paucity of data relating to aspirin.”
To fill this knowledge gap, the investigators recruited 17,598 participants from 33 countries who had stable peripheral artery disease and cardiovascular disease. Participants were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or a combination of 2.5-mg rivaroxaban twice daily with 100-mg aspirin once daily. This part of the trial was discontinued before completion because of early cardiovascular advantages associated with combination therapy over aspirin alone, and related findings were reported previously. While combination therapy did reduce cardiovascular risks, it had less favorable effects on gut health, highlighted by an associated increase in major GI bleeding events. Despite early cessation of the cardiovascular portion of the trial, the pantoprazole regimen was continued, offering a look at the effect of long-term PPI use on gut health.
At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. The primary efficacy outcome was time to first upper-GI clinical event, defined as a composite of the following: upper-GI obstruction, perforation, at least five gastroduodenal erosions with at least 3 days of GI pain, symptomatic gastroduodenal ulcer involving at least 3 days of GI pain, overt upper-GI bleeding of unknown origin, occult bleeding (drop in hemoglobin of at least 2 g/dL), overt bleeding with a gastroduodenal lesion (active bleeding during endoscopy), or a symptomatic gastroduodenal ulcer involving at least 3 days of GI pain. In addition to this measure, the investigators evaluated a post-hoc endpoint with a looser definition of peptic ulcer events, most notably eliminating the requirement that a lesion be actively bleeding during endoscopy.
Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking a nonsteroidal anti-inflammatory drug (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group, after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.
Analysis showed that upper-GI events occurred marginally less often in the pantoprazole group than the placebo group, but without statistical significance (1.2% vs. 1.3%; P = .35). Of the outcomes measured, only overt bleeding of gastroduodenal origin detected by radiography or endoscopy was statistically less common in the pantoprazole group than the placebo group, with a 48% reduced rate (0.2% vs. 0.4%; P = .03). No statistical efficacy differences or statistical interactions were detected between population subgroups.
“The data suggest that routine use of PPI therapy is not warranted for patients receiving low-dose rivaroxaban with or without aspirin for the prevention of atherothrombotic events in patients with stable coronary artery disease or symptomatic peripheral artery disease, as there was no overall impact on clinical upper-GI events or upper-GI bleeding,” the investigators wrote. “This is in contrast to previous systematic reviews of randomized trials reporting that PPIs were associated with a 50%-70% reduction in bleeding and symptomatic peptic ulcers related to nonsteroidal anti-inflammatory drugs, including in the critical care setting.”
Post-hoc analysis, which allowed for a broader definition of upper-GI events related to gastroduodenal ulcers, revealed a slightly greater reduction in risk of bleeding lesions in patients taking pantoprazole, compared with placebo (hazard ratio, 0.45), and additional risk reductions for peptic ulcers (HR, 0.46) and erosions (HR, 0.33). Ultimately, pantoprazole reduced the combined rate of post-hoc events by 56%.
The investigators noted that these ulcer- and erosion-reducing effects of pantoprazole align with previous reports. “It is therefore possible that PPIs might be beneficial for patients at particularly high risk for peptic ulcer disease who are also taking aspirin and/or anticoagulants,” the investigators concluded.
The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Allergan, Takeda, Janssen, and others.
SOURCE: Moayyedi P et al. Gastro. 2019 May 2. doi: 10.1053/j.gastro.2019.04.041.
FROM GASTROENTEROLOGY
POEM outperforms pneumatic dilation in randomized achalasia trial
Peroral endoscopic myotomy (POEM) had a success rate exceeding 90%, versus just about 50% for standard balloon dilation in what investigators say is, to their knowledge, the first-ever randomized trial to evaluate POEM as a first-line modality for this esophageal motility disorder.
Reflux esophagitis was the major downside of POEM, according to investigators, who reported the complication in 41% of patients at a 2-year follow-up, as compared to just 7% of patients undergoing the standard balloon dilation.
Nevertheless, there were no serious adverse events among 63 POEM-treated patients, while one patient out of 63 undergoing pneumatic dilation had a perforation that required endoscopic closure and hospitalization, according to senior study author Albert J. Bredenoord, MD, PhD, of Amsterdam University Medical Center.
“These findings support consideration of POEM as an initial treatment option for patients with achalasia,” Dr. Bredenoord and coinvestigators said in a report on the study appearing in JAMA.
While endoscopic pneumatic dilation is the usual treatment for achalasia, POEM has become more commonly used following case series showing high rates of efficacy, according to the authors.
The POEM procedure also offers advantages over laparoscopic Heller myotomy, which is invasive and associated with severe complications, including a transmural perforation rate of 4%-10%, they said in their report.
Their randomized trial included 133 adults with newly diagnosed achalasia enrolled at one of six hospitals in Germany, Hong Kong, Italy, Netherlands, and the United States.
Patients were randomly assigned to undergo 1-2 pneumatic dilations performed by an endoscopist who had performed at least 20 such procedures in the past, or to a POEM procedure likewise performed by an expert who had already done more than 20 such procedures.
At baseline, patients’ Eckardt symptom scores ranged from 6 to 9 on a scale with 0 indicating the lowest severity, to 12 indicating the highest. The median Eckardt scores were 8 in the POEM group and 7 in the pneumatic dilation group.
Treatment success, defined as an Eckardt score under 3 and no severe complications or retreatment at 2 years, was achieved by 58 of 63 patients (92%) in the POEM group, compared with 34 of 63 patients (54%) in the pneumatic dilation group (P less than .001), investigators reported.
Reflux esophagitis was observed in 22 of 54 POEM-treated patients (41%) who underwent endoscopy at a 2-year evaluation, compared with only 2 of 29 patients (7%) who had received the balloon dilation procedure (P = .002). In line with that finding, both reflux symptoms and daily proton pump inhibitor use were more common in the POEM group, investigators said.
However, there were no differences between POEM and pneumatic dilation groups in quality of life and other secondary endpoints, including median barium column height and median integrated relaxation pressure, they reported.
Two serious adverse events related to treatment were seen, according to investigators, including one perforation requiring an endoscopic closure plus antibiotics and hospitalization for 13 days, and one hospital admission for a night because of severe chest pain with no signs of perforation.
“Although POEM is more invasive and requires more technical endoscopic skills, the risk of severe complications was not higher than with pneumatic dilation, especially when performed by experienced endoscopists,” Dr. Bredenoord and coauthors said in their report.
However, these results do not imply that the traditional dilation procedure should be abandoned, they said, as POEM is more invasive, more involved, and more likely to result in reflux esophagitis.
“It seems reasonable to offer both options to treatment-naive patients with achalasia and counsel them to select treatment based on the patient’s characteristics, personal preference, comorbidity, and disease subtype,” they said.
Funding for the study came from Fonds NutsOhra and the European Society of Gastrointestinal Endoscopy. Dr. Bredenoord reported disclosures related to Norgine, Laborie, Medtronic, Diversatek, Nutricia, Regeneron, Celgene, Bayer, and Dr. Falk Pharma.
SOURCE: Ponds FA et al. JAMA. 2019;322(2):134-44. doi: 10.1001/jama.2019.8859.
Peroral endoscopic myotomy (POEM) had a success rate exceeding 90%, versus just about 50% for standard balloon dilation in what investigators say is, to their knowledge, the first-ever randomized trial to evaluate POEM as a first-line modality for this esophageal motility disorder.
Reflux esophagitis was the major downside of POEM, according to investigators, who reported the complication in 41% of patients at a 2-year follow-up, as compared to just 7% of patients undergoing the standard balloon dilation.
Nevertheless, there were no serious adverse events among 63 POEM-treated patients, while one patient out of 63 undergoing pneumatic dilation had a perforation that required endoscopic closure and hospitalization, according to senior study author Albert J. Bredenoord, MD, PhD, of Amsterdam University Medical Center.
“These findings support consideration of POEM as an initial treatment option for patients with achalasia,” Dr. Bredenoord and coinvestigators said in a report on the study appearing in JAMA.
While endoscopic pneumatic dilation is the usual treatment for achalasia, POEM has become more commonly used following case series showing high rates of efficacy, according to the authors.
The POEM procedure also offers advantages over laparoscopic Heller myotomy, which is invasive and associated with severe complications, including a transmural perforation rate of 4%-10%, they said in their report.
Their randomized trial included 133 adults with newly diagnosed achalasia enrolled at one of six hospitals in Germany, Hong Kong, Italy, Netherlands, and the United States.
Patients were randomly assigned to undergo 1-2 pneumatic dilations performed by an endoscopist who had performed at least 20 such procedures in the past, or to a POEM procedure likewise performed by an expert who had already done more than 20 such procedures.
At baseline, patients’ Eckardt symptom scores ranged from 6 to 9 on a scale with 0 indicating the lowest severity, to 12 indicating the highest. The median Eckardt scores were 8 in the POEM group and 7 in the pneumatic dilation group.
Treatment success, defined as an Eckardt score under 3 and no severe complications or retreatment at 2 years, was achieved by 58 of 63 patients (92%) in the POEM group, compared with 34 of 63 patients (54%) in the pneumatic dilation group (P less than .001), investigators reported.
Reflux esophagitis was observed in 22 of 54 POEM-treated patients (41%) who underwent endoscopy at a 2-year evaluation, compared with only 2 of 29 patients (7%) who had received the balloon dilation procedure (P = .002). In line with that finding, both reflux symptoms and daily proton pump inhibitor use were more common in the POEM group, investigators said.
However, there were no differences between POEM and pneumatic dilation groups in quality of life and other secondary endpoints, including median barium column height and median integrated relaxation pressure, they reported.
Two serious adverse events related to treatment were seen, according to investigators, including one perforation requiring an endoscopic closure plus antibiotics and hospitalization for 13 days, and one hospital admission for a night because of severe chest pain with no signs of perforation.
“Although POEM is more invasive and requires more technical endoscopic skills, the risk of severe complications was not higher than with pneumatic dilation, especially when performed by experienced endoscopists,” Dr. Bredenoord and coauthors said in their report.
However, these results do not imply that the traditional dilation procedure should be abandoned, they said, as POEM is more invasive, more involved, and more likely to result in reflux esophagitis.
“It seems reasonable to offer both options to treatment-naive patients with achalasia and counsel them to select treatment based on the patient’s characteristics, personal preference, comorbidity, and disease subtype,” they said.
Funding for the study came from Fonds NutsOhra and the European Society of Gastrointestinal Endoscopy. Dr. Bredenoord reported disclosures related to Norgine, Laborie, Medtronic, Diversatek, Nutricia, Regeneron, Celgene, Bayer, and Dr. Falk Pharma.
SOURCE: Ponds FA et al. JAMA. 2019;322(2):134-44. doi: 10.1001/jama.2019.8859.
Peroral endoscopic myotomy (POEM) had a success rate exceeding 90%, versus just about 50% for standard balloon dilation in what investigators say is, to their knowledge, the first-ever randomized trial to evaluate POEM as a first-line modality for this esophageal motility disorder.
Reflux esophagitis was the major downside of POEM, according to investigators, who reported the complication in 41% of patients at a 2-year follow-up, as compared to just 7% of patients undergoing the standard balloon dilation.
Nevertheless, there were no serious adverse events among 63 POEM-treated patients, while one patient out of 63 undergoing pneumatic dilation had a perforation that required endoscopic closure and hospitalization, according to senior study author Albert J. Bredenoord, MD, PhD, of Amsterdam University Medical Center.
“These findings support consideration of POEM as an initial treatment option for patients with achalasia,” Dr. Bredenoord and coinvestigators said in a report on the study appearing in JAMA.
While endoscopic pneumatic dilation is the usual treatment for achalasia, POEM has become more commonly used following case series showing high rates of efficacy, according to the authors.
The POEM procedure also offers advantages over laparoscopic Heller myotomy, which is invasive and associated with severe complications, including a transmural perforation rate of 4%-10%, they said in their report.
Their randomized trial included 133 adults with newly diagnosed achalasia enrolled at one of six hospitals in Germany, Hong Kong, Italy, Netherlands, and the United States.
Patients were randomly assigned to undergo 1-2 pneumatic dilations performed by an endoscopist who had performed at least 20 such procedures in the past, or to a POEM procedure likewise performed by an expert who had already done more than 20 such procedures.
At baseline, patients’ Eckardt symptom scores ranged from 6 to 9 on a scale with 0 indicating the lowest severity, to 12 indicating the highest. The median Eckardt scores were 8 in the POEM group and 7 in the pneumatic dilation group.
Treatment success, defined as an Eckardt score under 3 and no severe complications or retreatment at 2 years, was achieved by 58 of 63 patients (92%) in the POEM group, compared with 34 of 63 patients (54%) in the pneumatic dilation group (P less than .001), investigators reported.
Reflux esophagitis was observed in 22 of 54 POEM-treated patients (41%) who underwent endoscopy at a 2-year evaluation, compared with only 2 of 29 patients (7%) who had received the balloon dilation procedure (P = .002). In line with that finding, both reflux symptoms and daily proton pump inhibitor use were more common in the POEM group, investigators said.
However, there were no differences between POEM and pneumatic dilation groups in quality of life and other secondary endpoints, including median barium column height and median integrated relaxation pressure, they reported.
Two serious adverse events related to treatment were seen, according to investigators, including one perforation requiring an endoscopic closure plus antibiotics and hospitalization for 13 days, and one hospital admission for a night because of severe chest pain with no signs of perforation.
“Although POEM is more invasive and requires more technical endoscopic skills, the risk of severe complications was not higher than with pneumatic dilation, especially when performed by experienced endoscopists,” Dr. Bredenoord and coauthors said in their report.
However, these results do not imply that the traditional dilation procedure should be abandoned, they said, as POEM is more invasive, more involved, and more likely to result in reflux esophagitis.
“It seems reasonable to offer both options to treatment-naive patients with achalasia and counsel them to select treatment based on the patient’s characteristics, personal preference, comorbidity, and disease subtype,” they said.
Funding for the study came from Fonds NutsOhra and the European Society of Gastrointestinal Endoscopy. Dr. Bredenoord reported disclosures related to Norgine, Laborie, Medtronic, Diversatek, Nutricia, Regeneron, Celgene, Bayer, and Dr. Falk Pharma.
SOURCE: Ponds FA et al. JAMA. 2019;322(2):134-44. doi: 10.1001/jama.2019.8859.
FROM JAMA
Endoscopic treatment effective in T1b esophageal cancer
Findings from a systematic review may help guide treatment of patients with T1b esophageal cancer.
The review suggests that endoscopic submucosal dissection and endoscopic mucosal resection are appropriate for T1b esophageal cancers with a low risk of metastasis. The authors identified several factors associated with a higher risk of lymph node metastasis and said patients with these risk factors may benefit from adjuvant chemotherapy and radiation.
Mohamed O. Othman, MD, of Baylor College of Medicine, Houston, and colleagues conducted the review. Their report is in Clinical Gastroenterology and Hepatology.
The authors cited studies suggesting that survival rates would not be significantly different among early-stage esophageal cancer patients who undergo esophagectomy and those who receive endoscopic treatment, in the absence of lymph node metastasis. The risk of lymph node metastasis is higher in esophageal squamous cell carcinoma (ESCC) than in esophageal adenocarcinoma (EAC), and in those with deeper submucosal invasion (greater than 200 microm for ESCC or greater than 500 microm for EAC). Patients also have a higher risk of lymph node metastasis if they have poorly differentiated tumors, tumors larger than 2 cm, or lymphovascular invasion.
In the studies cited in the review, overall 5-year survival for esophageal squamous cell CA (ESCC) ranged from 68.6% (chemoradiation therapy alone) to 75% (endoscopic resection followed by chemoradiation), compared with 77.7% for surgery. For esophageal adenocarcinoma (EAC), there is less data but greater efficacy, with one study demonstrating 5-year overall survival of 93.9% in the ESD group compared with 97.3% in the surgery group. However, only approximately 15 patients in this study were diagnosed T1b.
The authors concluded that “ESD or EMR can be successfully applied to submucosal invasive cancers that have a low risk of metastatic potential....Future research should focus on novel biological and immunohistochemistry markers which can aid in the prediction of tumor behavior and lymph node metastasis status in T1b esophageal cancer.”
The authors disclosed relationships with Olympus, Boston Scientific, Lumendi, Aries Pharmaceutical, and Fujinon.
SOURCE: Othman MO et al. Clin Gastroenterol Hepatol 2019. doi: 10.1016/j.cgh.2019.05.045.
Findings from a systematic review may help guide treatment of patients with T1b esophageal cancer.
The review suggests that endoscopic submucosal dissection and endoscopic mucosal resection are appropriate for T1b esophageal cancers with a low risk of metastasis. The authors identified several factors associated with a higher risk of lymph node metastasis and said patients with these risk factors may benefit from adjuvant chemotherapy and radiation.
Mohamed O. Othman, MD, of Baylor College of Medicine, Houston, and colleagues conducted the review. Their report is in Clinical Gastroenterology and Hepatology.
The authors cited studies suggesting that survival rates would not be significantly different among early-stage esophageal cancer patients who undergo esophagectomy and those who receive endoscopic treatment, in the absence of lymph node metastasis. The risk of lymph node metastasis is higher in esophageal squamous cell carcinoma (ESCC) than in esophageal adenocarcinoma (EAC), and in those with deeper submucosal invasion (greater than 200 microm for ESCC or greater than 500 microm for EAC). Patients also have a higher risk of lymph node metastasis if they have poorly differentiated tumors, tumors larger than 2 cm, or lymphovascular invasion.
In the studies cited in the review, overall 5-year survival for esophageal squamous cell CA (ESCC) ranged from 68.6% (chemoradiation therapy alone) to 75% (endoscopic resection followed by chemoradiation), compared with 77.7% for surgery. For esophageal adenocarcinoma (EAC), there is less data but greater efficacy, with one study demonstrating 5-year overall survival of 93.9% in the ESD group compared with 97.3% in the surgery group. However, only approximately 15 patients in this study were diagnosed T1b.
The authors concluded that “ESD or EMR can be successfully applied to submucosal invasive cancers that have a low risk of metastatic potential....Future research should focus on novel biological and immunohistochemistry markers which can aid in the prediction of tumor behavior and lymph node metastasis status in T1b esophageal cancer.”
The authors disclosed relationships with Olympus, Boston Scientific, Lumendi, Aries Pharmaceutical, and Fujinon.
SOURCE: Othman MO et al. Clin Gastroenterol Hepatol 2019. doi: 10.1016/j.cgh.2019.05.045.
Findings from a systematic review may help guide treatment of patients with T1b esophageal cancer.
The review suggests that endoscopic submucosal dissection and endoscopic mucosal resection are appropriate for T1b esophageal cancers with a low risk of metastasis. The authors identified several factors associated with a higher risk of lymph node metastasis and said patients with these risk factors may benefit from adjuvant chemotherapy and radiation.
Mohamed O. Othman, MD, of Baylor College of Medicine, Houston, and colleagues conducted the review. Their report is in Clinical Gastroenterology and Hepatology.
The authors cited studies suggesting that survival rates would not be significantly different among early-stage esophageal cancer patients who undergo esophagectomy and those who receive endoscopic treatment, in the absence of lymph node metastasis. The risk of lymph node metastasis is higher in esophageal squamous cell carcinoma (ESCC) than in esophageal adenocarcinoma (EAC), and in those with deeper submucosal invasion (greater than 200 microm for ESCC or greater than 500 microm for EAC). Patients also have a higher risk of lymph node metastasis if they have poorly differentiated tumors, tumors larger than 2 cm, or lymphovascular invasion.
In the studies cited in the review, overall 5-year survival for esophageal squamous cell CA (ESCC) ranged from 68.6% (chemoradiation therapy alone) to 75% (endoscopic resection followed by chemoradiation), compared with 77.7% for surgery. For esophageal adenocarcinoma (EAC), there is less data but greater efficacy, with one study demonstrating 5-year overall survival of 93.9% in the ESD group compared with 97.3% in the surgery group. However, only approximately 15 patients in this study were diagnosed T1b.
The authors concluded that “ESD or EMR can be successfully applied to submucosal invasive cancers that have a low risk of metastatic potential....Future research should focus on novel biological and immunohistochemistry markers which can aid in the prediction of tumor behavior and lymph node metastasis status in T1b esophageal cancer.”
The authors disclosed relationships with Olympus, Boston Scientific, Lumendi, Aries Pharmaceutical, and Fujinon.
SOURCE: Othman MO et al. Clin Gastroenterol Hepatol 2019. doi: 10.1016/j.cgh.2019.05.045.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Budesonide tablets considerably outperformed placebo for active EoE
Budesonide orodispersible tablets (BOTs) are highly effective in inducing disease remission in adults with active eosinophilic esophagitis (EOE), according to a study of the tablets versus placebo in European patients.
“A 6-week treatment with 1 mg budesonide twice daily was highly superior over placebo with regard to all predefined primary and secondary outcomes,” wrote Alfredo J. Lucendo, MD, of Hospital General de Tomelloso in Real, Spain, and his coauthors. The study was published in Gastroenterology.
To assess the effectiveness and tolerability of BOT in adults with EOE, Dr. Lucendo and his fellow researchers launched a randomized, placebo-controlled trial made up of 88 European adults with active EoE. Patients were assigned to either a group that received BOT twice daily (n = 59) or a group that received placebo (n = 29). The primary endpoint was complete remission.
After 6 weeks, 34 of 59 patients (58%) receiving BOT had achieved complete remission, compared with 0 patients receiving placebo (P less than .0001). After 12 weeks, 50 of 59 patients (85%) in the BOT group had achieved complete remission. BOT was also well tolerated; no serious adverse event was reported, and no differences were observed between groups with regard to commonly reported adverse events.
The coauthors acknowledged their study’s limitations, including the fact that it was designed to demonstrate budesonide’s superiority to placebo at 6 weeks, not to identify the time of its maximal effect. In addition, the researchers did not identify a minimally effective dose; they did, however, note their belief that a lower dose could still achieve similar rates of remission and “a higher dose would not achieve a higher clinico-remission rate.”
The study was funded by Dr. Falk Pharma. The authors reported numerous conflicts of interest, including receiving research funding and speaker fees from various pharmaceutical companies and foundations.
SOURCE: Lucendo AJ et al. Gastroenterology. 2019 Mar 25. doi: 10.1053/j.gastro.2019.03.025.
Budesonide orodispersible tablets (BOTs) are highly effective in inducing disease remission in adults with active eosinophilic esophagitis (EOE), according to a study of the tablets versus placebo in European patients.
“A 6-week treatment with 1 mg budesonide twice daily was highly superior over placebo with regard to all predefined primary and secondary outcomes,” wrote Alfredo J. Lucendo, MD, of Hospital General de Tomelloso in Real, Spain, and his coauthors. The study was published in Gastroenterology.
To assess the effectiveness and tolerability of BOT in adults with EOE, Dr. Lucendo and his fellow researchers launched a randomized, placebo-controlled trial made up of 88 European adults with active EoE. Patients were assigned to either a group that received BOT twice daily (n = 59) or a group that received placebo (n = 29). The primary endpoint was complete remission.
After 6 weeks, 34 of 59 patients (58%) receiving BOT had achieved complete remission, compared with 0 patients receiving placebo (P less than .0001). After 12 weeks, 50 of 59 patients (85%) in the BOT group had achieved complete remission. BOT was also well tolerated; no serious adverse event was reported, and no differences were observed between groups with regard to commonly reported adverse events.
The coauthors acknowledged their study’s limitations, including the fact that it was designed to demonstrate budesonide’s superiority to placebo at 6 weeks, not to identify the time of its maximal effect. In addition, the researchers did not identify a minimally effective dose; they did, however, note their belief that a lower dose could still achieve similar rates of remission and “a higher dose would not achieve a higher clinico-remission rate.”
The study was funded by Dr. Falk Pharma. The authors reported numerous conflicts of interest, including receiving research funding and speaker fees from various pharmaceutical companies and foundations.
SOURCE: Lucendo AJ et al. Gastroenterology. 2019 Mar 25. doi: 10.1053/j.gastro.2019.03.025.
Budesonide orodispersible tablets (BOTs) are highly effective in inducing disease remission in adults with active eosinophilic esophagitis (EOE), according to a study of the tablets versus placebo in European patients.
“A 6-week treatment with 1 mg budesonide twice daily was highly superior over placebo with regard to all predefined primary and secondary outcomes,” wrote Alfredo J. Lucendo, MD, of Hospital General de Tomelloso in Real, Spain, and his coauthors. The study was published in Gastroenterology.
To assess the effectiveness and tolerability of BOT in adults with EOE, Dr. Lucendo and his fellow researchers launched a randomized, placebo-controlled trial made up of 88 European adults with active EoE. Patients were assigned to either a group that received BOT twice daily (n = 59) or a group that received placebo (n = 29). The primary endpoint was complete remission.
After 6 weeks, 34 of 59 patients (58%) receiving BOT had achieved complete remission, compared with 0 patients receiving placebo (P less than .0001). After 12 weeks, 50 of 59 patients (85%) in the BOT group had achieved complete remission. BOT was also well tolerated; no serious adverse event was reported, and no differences were observed between groups with regard to commonly reported adverse events.
The coauthors acknowledged their study’s limitations, including the fact that it was designed to demonstrate budesonide’s superiority to placebo at 6 weeks, not to identify the time of its maximal effect. In addition, the researchers did not identify a minimally effective dose; they did, however, note their belief that a lower dose could still achieve similar rates of remission and “a higher dose would not achieve a higher clinico-remission rate.”
The study was funded by Dr. Falk Pharma. The authors reported numerous conflicts of interest, including receiving research funding and speaker fees from various pharmaceutical companies and foundations.
SOURCE: Lucendo AJ et al. Gastroenterology. 2019 Mar 25. doi: 10.1053/j.gastro.2019.03.025.
FROM GASTROENTEROLOGY
Barrett’s esophagus endoscopies are undersampled
As many as one in five endoscopies in patients with Barrett’s esophagus are not being done according to accepted protocol, say the authors of a study published online in Gastrointestinal Endoscopy.
The Seattle biopsy protocol, which is recommended in nondysplastic Barrett’s esophagus to pick up esophageal adenocarcinoma, calls for four-quadrant biopsies at 2-cm intervals in patients without dysplasia and 1-cm intervals in patients with prior dysplasia, as well as targeted biopsies of any mucosal abnormalities.
Sachin Wani, MD, from the University of Colorado at Denver, Aurora, and coauthors used registry data to examine procedures and outcomes in 58,709 esophagogastroduodenoscopies in 53,541 patients with an endoscopic finding of, or screening indication for, Barrett’s esophagus.
They assessed protocol adherence by dividing the Barrett’s esophagus length by the number of pathology jars. A ratio of two or less was considered adherent, and the authors also allowed for a lenient rounding down, or stringent rounding up.
Just over half the procedures in the study (51.1%) resulted in a recorded, pathology-confirmed diagnosis of Barrett’s esophagus, and the mean length of Barrett’s esophagus was 2.3 cm.
Overall, 87.8% of endoscopies were adherent according to the lenient criteria, and 82.7% were adherent by the stringent definition.
Patients with longer lengths of Barrett’s esophagus were significantly less likely to be biopsied according to the Seattle biopsy protocol guidelines, with a 31% decrease in odds of adherence with every 1-cm increase in Barrett’s esophagus length. Patients with lengths from 0-4 cm were 76.3%-80.6% adherent to biopsy protocols, but those with lengths greater than 8 cm were only 37.9%-40.6% adherent.
“These results are most concerning because we found that dysplasia detection rates also increase with increasing [Barrett’s esophagus] length,” the authors wrote. “Therefore, per unit length, patients who need it most are being biopsied least.
Older and male patients also were less likely to be biopsied according to the protocol, and an American Society of Anesthesiologists classification of three or above was a predictor of nonadherence.
“These findings may be a reflection of a higher number of comorbidities in these patients with [Barrett’s esophagus] and perceived lack of benefit of surveillance endoscopy,” the authors wrote.
They also noted a geographic effect, such that patients living in the Northeast regions were more likely to be biopsied according to protocol than were those living in Western regions.
The study was funded by the University of Colorado department of medicine. Four authors declared consultancies and research grants from the medical device sector and others.
SOURCE: Wani S et al. Gastrointest Endosc. 2019, June 11.
As many as one in five endoscopies in patients with Barrett’s esophagus are not being done according to accepted protocol, say the authors of a study published online in Gastrointestinal Endoscopy.
The Seattle biopsy protocol, which is recommended in nondysplastic Barrett’s esophagus to pick up esophageal adenocarcinoma, calls for four-quadrant biopsies at 2-cm intervals in patients without dysplasia and 1-cm intervals in patients with prior dysplasia, as well as targeted biopsies of any mucosal abnormalities.
Sachin Wani, MD, from the University of Colorado at Denver, Aurora, and coauthors used registry data to examine procedures and outcomes in 58,709 esophagogastroduodenoscopies in 53,541 patients with an endoscopic finding of, or screening indication for, Barrett’s esophagus.
They assessed protocol adherence by dividing the Barrett’s esophagus length by the number of pathology jars. A ratio of two or less was considered adherent, and the authors also allowed for a lenient rounding down, or stringent rounding up.
Just over half the procedures in the study (51.1%) resulted in a recorded, pathology-confirmed diagnosis of Barrett’s esophagus, and the mean length of Barrett’s esophagus was 2.3 cm.
Overall, 87.8% of endoscopies were adherent according to the lenient criteria, and 82.7% were adherent by the stringent definition.
Patients with longer lengths of Barrett’s esophagus were significantly less likely to be biopsied according to the Seattle biopsy protocol guidelines, with a 31% decrease in odds of adherence with every 1-cm increase in Barrett’s esophagus length. Patients with lengths from 0-4 cm were 76.3%-80.6% adherent to biopsy protocols, but those with lengths greater than 8 cm were only 37.9%-40.6% adherent.
“These results are most concerning because we found that dysplasia detection rates also increase with increasing [Barrett’s esophagus] length,” the authors wrote. “Therefore, per unit length, patients who need it most are being biopsied least.
Older and male patients also were less likely to be biopsied according to the protocol, and an American Society of Anesthesiologists classification of three or above was a predictor of nonadherence.
“These findings may be a reflection of a higher number of comorbidities in these patients with [Barrett’s esophagus] and perceived lack of benefit of surveillance endoscopy,” the authors wrote.
They also noted a geographic effect, such that patients living in the Northeast regions were more likely to be biopsied according to protocol than were those living in Western regions.
The study was funded by the University of Colorado department of medicine. Four authors declared consultancies and research grants from the medical device sector and others.
SOURCE: Wani S et al. Gastrointest Endosc. 2019, June 11.
As many as one in five endoscopies in patients with Barrett’s esophagus are not being done according to accepted protocol, say the authors of a study published online in Gastrointestinal Endoscopy.
The Seattle biopsy protocol, which is recommended in nondysplastic Barrett’s esophagus to pick up esophageal adenocarcinoma, calls for four-quadrant biopsies at 2-cm intervals in patients without dysplasia and 1-cm intervals in patients with prior dysplasia, as well as targeted biopsies of any mucosal abnormalities.
Sachin Wani, MD, from the University of Colorado at Denver, Aurora, and coauthors used registry data to examine procedures and outcomes in 58,709 esophagogastroduodenoscopies in 53,541 patients with an endoscopic finding of, or screening indication for, Barrett’s esophagus.
They assessed protocol adherence by dividing the Barrett’s esophagus length by the number of pathology jars. A ratio of two or less was considered adherent, and the authors also allowed for a lenient rounding down, or stringent rounding up.
Just over half the procedures in the study (51.1%) resulted in a recorded, pathology-confirmed diagnosis of Barrett’s esophagus, and the mean length of Barrett’s esophagus was 2.3 cm.
Overall, 87.8% of endoscopies were adherent according to the lenient criteria, and 82.7% were adherent by the stringent definition.
Patients with longer lengths of Barrett’s esophagus were significantly less likely to be biopsied according to the Seattle biopsy protocol guidelines, with a 31% decrease in odds of adherence with every 1-cm increase in Barrett’s esophagus length. Patients with lengths from 0-4 cm were 76.3%-80.6% adherent to biopsy protocols, but those with lengths greater than 8 cm were only 37.9%-40.6% adherent.
“These results are most concerning because we found that dysplasia detection rates also increase with increasing [Barrett’s esophagus] length,” the authors wrote. “Therefore, per unit length, patients who need it most are being biopsied least.
Older and male patients also were less likely to be biopsied according to the protocol, and an American Society of Anesthesiologists classification of three or above was a predictor of nonadherence.
“These findings may be a reflection of a higher number of comorbidities in these patients with [Barrett’s esophagus] and perceived lack of benefit of surveillance endoscopy,” the authors wrote.
They also noted a geographic effect, such that patients living in the Northeast regions were more likely to be biopsied according to protocol than were those living in Western regions.
The study was funded by the University of Colorado department of medicine. Four authors declared consultancies and research grants from the medical device sector and others.
SOURCE: Wani S et al. Gastrointest Endosc. 2019, June 11.
FROM GASTROINTESTINAL ENDOSCOPY
Rivaroxaban tied to higher GI bleeding than other NOACs
SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.
“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”
Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.
Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.
During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).
Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).
When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.
SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.
“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”
Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.
Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.
During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).
Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).
When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.
SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.
“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”
Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.
Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.
During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).
Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).
When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.
REPORTING FROM DDW 2019
Updated systematic review of aspirin primary prevention shows benefits, risks
Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.
“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.
The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.
This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.
The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).
As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.
The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).
The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.
The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.
The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.
Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
On Twitter @mitchelzoler
SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.
The three trials published in 2018 that added important new data on primary prevention for cardiovascular disease with aspirin must ideally be interpreted within the context of the totality of evidence on this subject. This was achieved in the analysis reported by Dr. Mehta and his associates, as well as in other more recent publications.
Making a decision about using aspirin for primary prevention in individuals based on trial data is very challenging because it requires weighing a modest potential benefit that people gain from daily aspirin for preventing a first cardiovascular event against the modest risk of an adverse bleeding event. It does not suffice simply to compare the number of cardiovascular and bleeding events, because those two types of events do not have the same immediate or long-term consequences. Each patient must make a personal choice between the risks and benefits.
The greatest potential benefit from aspirin prophylaxis seems to be in people with increased cardiovascular risk but with no increased bleeding risk. In general, this means people aged 50-59 years old, and also possibly those aged 60-69 years old if their estimated 10-year cardiovascular disease risk is more than 10%. It may make more sense to first focus on other risk-reducing steps, such as smoking cessation, blood pressure control, and statin treatment. After that, prophylactic aspirin may be reasonable for people who retain a 10-year cardiovascular disease risk of more than 10% who are also not at increased bleeding risk. That seems to make it prudent to avoid aspirin for primary prevention once people reach the age of 70 years, although people who have been taking aspirin safely for a period of time before reaching 70 might reasonably consider continuing the prophylaxis for a period of time.
This and similar reviews continue to have major limitations. The duration of the trials they reviewed, a mean of 6.4 years, is insufficient to understand the full effect from aspirin prophylaxis. Also, none of the recent reviews used a patient-level meta-analysis, which could better help us understand aspirin’s action in key subgroups, such as women, patients with diabetes, and patients on treatments such as statins that reduce their cardiovascular risk.
Michael Pignone, MD, is professor and chair of medicine at the University of Texas Dell Medical School in Austin. He had no disclosures. He made these comments in an editorial that accompanied the report (J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.502).
The three trials published in 2018 that added important new data on primary prevention for cardiovascular disease with aspirin must ideally be interpreted within the context of the totality of evidence on this subject. This was achieved in the analysis reported by Dr. Mehta and his associates, as well as in other more recent publications.
Making a decision about using aspirin for primary prevention in individuals based on trial data is very challenging because it requires weighing a modest potential benefit that people gain from daily aspirin for preventing a first cardiovascular event against the modest risk of an adverse bleeding event. It does not suffice simply to compare the number of cardiovascular and bleeding events, because those two types of events do not have the same immediate or long-term consequences. Each patient must make a personal choice between the risks and benefits.
The greatest potential benefit from aspirin prophylaxis seems to be in people with increased cardiovascular risk but with no increased bleeding risk. In general, this means people aged 50-59 years old, and also possibly those aged 60-69 years old if their estimated 10-year cardiovascular disease risk is more than 10%. It may make more sense to first focus on other risk-reducing steps, such as smoking cessation, blood pressure control, and statin treatment. After that, prophylactic aspirin may be reasonable for people who retain a 10-year cardiovascular disease risk of more than 10% who are also not at increased bleeding risk. That seems to make it prudent to avoid aspirin for primary prevention once people reach the age of 70 years, although people who have been taking aspirin safely for a period of time before reaching 70 might reasonably consider continuing the prophylaxis for a period of time.
This and similar reviews continue to have major limitations. The duration of the trials they reviewed, a mean of 6.4 years, is insufficient to understand the full effect from aspirin prophylaxis. Also, none of the recent reviews used a patient-level meta-analysis, which could better help us understand aspirin’s action in key subgroups, such as women, patients with diabetes, and patients on treatments such as statins that reduce their cardiovascular risk.
Michael Pignone, MD, is professor and chair of medicine at the University of Texas Dell Medical School in Austin. He had no disclosures. He made these comments in an editorial that accompanied the report (J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.502).
The three trials published in 2018 that added important new data on primary prevention for cardiovascular disease with aspirin must ideally be interpreted within the context of the totality of evidence on this subject. This was achieved in the analysis reported by Dr. Mehta and his associates, as well as in other more recent publications.
Making a decision about using aspirin for primary prevention in individuals based on trial data is very challenging because it requires weighing a modest potential benefit that people gain from daily aspirin for preventing a first cardiovascular event against the modest risk of an adverse bleeding event. It does not suffice simply to compare the number of cardiovascular and bleeding events, because those two types of events do not have the same immediate or long-term consequences. Each patient must make a personal choice between the risks and benefits.
The greatest potential benefit from aspirin prophylaxis seems to be in people with increased cardiovascular risk but with no increased bleeding risk. In general, this means people aged 50-59 years old, and also possibly those aged 60-69 years old if their estimated 10-year cardiovascular disease risk is more than 10%. It may make more sense to first focus on other risk-reducing steps, such as smoking cessation, blood pressure control, and statin treatment. After that, prophylactic aspirin may be reasonable for people who retain a 10-year cardiovascular disease risk of more than 10% who are also not at increased bleeding risk. That seems to make it prudent to avoid aspirin for primary prevention once people reach the age of 70 years, although people who have been taking aspirin safely for a period of time before reaching 70 might reasonably consider continuing the prophylaxis for a period of time.
This and similar reviews continue to have major limitations. The duration of the trials they reviewed, a mean of 6.4 years, is insufficient to understand the full effect from aspirin prophylaxis. Also, none of the recent reviews used a patient-level meta-analysis, which could better help us understand aspirin’s action in key subgroups, such as women, patients with diabetes, and patients on treatments such as statins that reduce their cardiovascular risk.
Michael Pignone, MD, is professor and chair of medicine at the University of Texas Dell Medical School in Austin. He had no disclosures. He made these comments in an editorial that accompanied the report (J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.502).
Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.
“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.
The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.
This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.
The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).
As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.
The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).
The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.
The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.
The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.
Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
On Twitter @mitchelzoler
SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.
Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.
“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.
The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.
This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.
The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).
As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.
The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).
The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.
The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.
The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.
Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
On Twitter @mitchelzoler
SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.
FROM JACC
Key clinical point: Cumulative trial results continue to show that aspirin primary prevention cuts CVD events while boosting major bleeds.
Major finding: Aspirin prophylaxis cut cardiovascular events with an NNT of 263, but increased major bleeds with an NNH of 222.
Study details: Systematic review of data from 165,502 people enrolled in 15 randomized trials.
Disclosures: Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
Source: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.