Upper GI Tract

HONOLULU – A survey of almost 500 physicians found that primary care physicians (PCPs) are far more concerned about the reported adverse effects of proton pump inhibitors (PPIs) than are gastroenterologists and use them more sparingly. The results of the survey were presented at the 2015 American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course.

“We asked physicians about a broad array of adverse effects from long-term use of PPIs and PCPs expressed greater concern for all of them,” reported Dr. Samir Kapadia, division of gastroenterology and hepatology, State University of New York at Stony Brook. “Alternatively, significantly more gastroenterologists responded that they really had no concerns for any of these adverse effects.”

© nebari/Thinkstock

The evidence may be on the side of the gastroenterologists, according to Dr. Kapadia. Although PPIs have been associated with hypomagnesemia, iron deficiency, vitamin B₁₂ deficiency, diarrhea caused by Clostridium difficile infection, and interactions with the platelet inhibitor clopidogrel, Dr. Kapadia noted that few associations have been made on the basis of prospective trials.

“Much of the available literature is observational or based on studies that are heterogeneous and small,” Dr. Kapadia. “Confounding factors in these studies also limit interpretation.”

In this study for which surveys are still being collected, a 19-item questionnaire was distributed to 384 gastroenterologists and 88 PCPs. In addition to demographic information, the surveys were designed to capture opinions about the safety of PPIs as well as elicit information about how these agents are being used in clinical practice.

Of side effects associated with PPIs, significantly more PCPs than gastroenterologists expressed concern about hypomagnesemia (41.7% vs. 6.3%; P less than .001), iron deficiency (33.3% vs. 11.4%; P = .014) and vitamin B₁₂ deficiency (47.6% vs. 17.3%; P = .005). From the other perspective, when asked about their concern for these and other safety issues, the answer was “none of the above” for 26.2% of PCPs and 67.1% of gastroenterologists (P less than .001).

When given specific risk scenarios, PCPs were consistently more prepared to discontinue PPI therapy than were gastroenterologists. For example, in a hypothetical 65-year-old with GERD symptoms expressing concern about risk of hip fracture, 64.5% of PCPs vs. 30.7% of gastroenterologists (P less than .001) responded that they would discontinue the PPI. In a patient of the same age about to start broad-spectrum antibiotics for cellulitis, 16.1% of PCPs, but only 4.3% of gastroenterologists (P = .001) reported that they would discontinue PPIs. Conversely, 68.5% of gastroenterologists vs. 54.2% of PCPs (P = .028) would continue therapy.

For a hypothetical 65-year-old with symptomatic gastroesophageal reflux disease (GERD) initiating clopidogrel, 50% of PCPs vs. 27.6% of gastroenterologists (P = .001) would switch to an H₂-receptor antagonist. Only 27.3% of PCPs vs. 46.4% of gastroenterologists (P = .001) would continue the PPI. When the age of the hypothetical patient is raised to 75 years, PCPs, but not gastroenterologists, were even more likely to discontinue PPI therapy.

Using PPIs appropriately is an important goal, Dr. Kapadia emphasized. However, he suggested that many warnings about the risks of PPIs, including those issued by the Food and Drug Administration, are incompletely substantiated and are not being evaluated with an appropriate attention to benefit-to-risk ratio of a drug that not only controls symptoms but may also reduce risk of GI bleeding. Others share this point of view.

“The pendulum has moved too far in regard to the fear of potential side effects,” agreed Dr. Philip Katz, chairman, division of gastroenterology, Albert Einstein Medical Center, Philadelphia. First author of the 2013 ACG guidelines on GERD, which addresses the safety of PPIs (Am J Gastroenterol. 2013;108:308-28), Dr. Katz said in an interview that the data generated by this survey suggest that PCPs are misinterpreting the relative risks and need to be given more information about indications in which benefits are well established.

Making the same point, Dr. Nicholas J. Shaheen, chief, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill, suggested “This may be a failure on our part [as gastroenterologists] to educate our colleagues about the role of these drugs.”

Dr. Kapadia reported no potential conflicts.

HONOLULU – A survey of almost 500 physicians found that primary care physicians (PCPs) are far more concerned about the reported adverse effects of proton pump inhibitors (PPIs) than are gastroenterologists and use them more sparingly. The results of the survey were presented at the 2015 American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course.

“We asked physicians about a broad array of adverse effects from long-term use of PPIs and PCPs expressed greater concern for all of them,” reported Dr. Samir Kapadia, division of gastroenterology and hepatology, State University of New York at Stony Brook. “Alternatively, significantly more gastroenterologists responded that they really had no concerns for any of these adverse effects.”

© nebari/Thinkstock

The evidence may be on the side of the gastroenterologists, according to Dr. Kapadia. Although PPIs have been associated with hypomagnesemia, iron deficiency, vitamin B₁₂ deficiency, diarrhea caused by Clostridium difficile infection, and interactions with the platelet inhibitor clopidogrel, Dr. Kapadia noted that few associations have been made on the basis of prospective trials.

“Much of the available literature is observational or based on studies that are heterogeneous and small,” Dr. Kapadia. “Confounding factors in these studies also limit interpretation.”

In this study for which surveys are still being collected, a 19-item questionnaire was distributed to 384 gastroenterologists and 88 PCPs. In addition to demographic information, the surveys were designed to capture opinions about the safety of PPIs as well as elicit information about how these agents are being used in clinical practice.

Of side effects associated with PPIs, significantly more PCPs than gastroenterologists expressed concern about hypomagnesemia (41.7% vs. 6.3%; P less than .001), iron deficiency (33.3% vs. 11.4%; P = .014) and vitamin B₁₂ deficiency (47.6% vs. 17.3%; P = .005). From the other perspective, when asked about their concern for these and other safety issues, the answer was “none of the above” for 26.2% of PCPs and 67.1% of gastroenterologists (P less than .001).

When given specific risk scenarios, PCPs were consistently more prepared to discontinue PPI therapy than were gastroenterologists. For example, in a hypothetical 65-year-old with GERD symptoms expressing concern about risk of hip fracture, 64.5% of PCPs vs. 30.7% of gastroenterologists (P less than .001) responded that they would discontinue the PPI. In a patient of the same age about to start broad-spectrum antibiotics for cellulitis, 16.1% of PCPs, but only 4.3% of gastroenterologists (P = .001) reported that they would discontinue PPIs. Conversely, 68.5% of gastroenterologists vs. 54.2% of PCPs (P = .028) would continue therapy.

For a hypothetical 65-year-old with symptomatic gastroesophageal reflux disease (GERD) initiating clopidogrel, 50% of PCPs vs. 27.6% of gastroenterologists (P = .001) would switch to an H₂-receptor antagonist. Only 27.3% of PCPs vs. 46.4% of gastroenterologists (P = .001) would continue the PPI. When the age of the hypothetical patient is raised to 75 years, PCPs, but not gastroenterologists, were even more likely to discontinue PPI therapy.

Using PPIs appropriately is an important goal, Dr. Kapadia emphasized. However, he suggested that many warnings about the risks of PPIs, including those issued by the Food and Drug Administration, are incompletely substantiated and are not being evaluated with an appropriate attention to benefit-to-risk ratio of a drug that not only controls symptoms but may also reduce risk of GI bleeding. Others share this point of view.

“The pendulum has moved too far in regard to the fear of potential side effects,” agreed Dr. Philip Katz, chairman, division of gastroenterology, Albert Einstein Medical Center, Philadelphia. First author of the 2013 ACG guidelines on GERD, which addresses the safety of PPIs (Am J Gastroenterol. 2013;108:308-28), Dr. Katz said in an interview that the data generated by this survey suggest that PCPs are misinterpreting the relative risks and need to be given more information about indications in which benefits are well established.

Making the same point, Dr. Nicholas J. Shaheen, chief, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill, suggested “This may be a failure on our part [as gastroenterologists] to educate our colleagues about the role of these drugs.”

Dr. Kapadia reported no potential conflicts.

HONOLULU – A survey of almost 500 physicians found that primary care physicians (PCPs) are far more concerned about the reported adverse effects of proton pump inhibitors (PPIs) than are gastroenterologists and use them more sparingly. The results of the survey were presented at the 2015 American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course.

“We asked physicians about a broad array of adverse effects from long-term use of PPIs and PCPs expressed greater concern for all of them,” reported Dr. Samir Kapadia, division of gastroenterology and hepatology, State University of New York at Stony Brook. “Alternatively, significantly more gastroenterologists responded that they really had no concerns for any of these adverse effects.”

© nebari/Thinkstock

The evidence may be on the side of the gastroenterologists, according to Dr. Kapadia. Although PPIs have been associated with hypomagnesemia, iron deficiency, vitamin B₁₂ deficiency, diarrhea caused by Clostridium difficile infection, and interactions with the platelet inhibitor clopidogrel, Dr. Kapadia noted that few associations have been made on the basis of prospective trials.

“Much of the available literature is observational or based on studies that are heterogeneous and small,” Dr. Kapadia. “Confounding factors in these studies also limit interpretation.”

In this study for which surveys are still being collected, a 19-item questionnaire was distributed to 384 gastroenterologists and 88 PCPs. In addition to demographic information, the surveys were designed to capture opinions about the safety of PPIs as well as elicit information about how these agents are being used in clinical practice.

Of side effects associated with PPIs, significantly more PCPs than gastroenterologists expressed concern about hypomagnesemia (41.7% vs. 6.3%; P less than .001), iron deficiency (33.3% vs. 11.4%; P = .014) and vitamin B₁₂ deficiency (47.6% vs. 17.3%; P = .005). From the other perspective, when asked about their concern for these and other safety issues, the answer was “none of the above” for 26.2% of PCPs and 67.1% of gastroenterologists (P less than .001).

When given specific risk scenarios, PCPs were consistently more prepared to discontinue PPI therapy than were gastroenterologists. For example, in a hypothetical 65-year-old with GERD symptoms expressing concern about risk of hip fracture, 64.5% of PCPs vs. 30.7% of gastroenterologists (P less than .001) responded that they would discontinue the PPI. In a patient of the same age about to start broad-spectrum antibiotics for cellulitis, 16.1% of PCPs, but only 4.3% of gastroenterologists (P = .001) reported that they would discontinue PPIs. Conversely, 68.5% of gastroenterologists vs. 54.2% of PCPs (P = .028) would continue therapy.

For a hypothetical 65-year-old with symptomatic gastroesophageal reflux disease (GERD) initiating clopidogrel, 50% of PCPs vs. 27.6% of gastroenterologists (P = .001) would switch to an H₂-receptor antagonist. Only 27.3% of PCPs vs. 46.4% of gastroenterologists (P = .001) would continue the PPI. When the age of the hypothetical patient is raised to 75 years, PCPs, but not gastroenterologists, were even more likely to discontinue PPI therapy.

Using PPIs appropriately is an important goal, Dr. Kapadia emphasized. However, he suggested that many warnings about the risks of PPIs, including those issued by the Food and Drug Administration, are incompletely substantiated and are not being evaluated with an appropriate attention to benefit-to-risk ratio of a drug that not only controls symptoms but may also reduce risk of GI bleeding. Others share this point of view.

“The pendulum has moved too far in regard to the fear of potential side effects,” agreed Dr. Philip Katz, chairman, division of gastroenterology, Albert Einstein Medical Center, Philadelphia. First author of the 2013 ACG guidelines on GERD, which addresses the safety of PPIs (Am J Gastroenterol. 2013;108:308-28), Dr. Katz said in an interview that the data generated by this survey suggest that PCPs are misinterpreting the relative risks and need to be given more information about indications in which benefits are well established.

Making the same point, Dr. Nicholas J. Shaheen, chief, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill, suggested “This may be a failure on our part [as gastroenterologists] to educate our colleagues about the role of these drugs.”

Dr. Kapadia reported no potential conflicts.

HONOLULU – Obese patients who develop an upper GI bleed receive more treatment, are more likely to develop hemorrhagic shock, and are more likely to require admission to an intensive care unit than those who are not obese, but they do not have higher in-hospital mortality, according to analysis of a large national database that was presented at the annual meeting of the American College of Gastroenterology.

The significantly greater odds ratio of most major complications from upper GI bleeds in patients with obesity relative to those who are not obese was expected but so was an increased rate of in-hospital mortality, according to the first author of the study, Dr. Marwan S. Abou Gergi of Catalyst Medical Consulting, Baltimore.

Courtesy Wikimedia Commons/Med Chaos/Creative Commons 1.0

“In this study, patients with obesity received more frequent endoscopic interventions, which could explain why mortality rates were not significantly higher,” Dr. Abou Gergi reported.

In the analysis, characterized as the first study to evaluate the impact of obesity on outcomes in upper GI hemorrhage, data were drawn from the 2012 Nationwide Inpatient Sample database, which is considered to provide a representative sample of U.S. hospital experience. Drawn from more than 7 million hospitalizations, the study focused on patients 18 or over with a primary ICD-9 code for upper GI hemorrhage. The primary outcome was mortality. Secondary outcomes included interventions, ICU admissions, and length of stay.

Of the 132,545 discharges with upper GI hemorrhage, 11,220 (8.5%) were identified as obese. The in-hospital mortality overall was 1.97%, but the proportion of those who died was slightly lower among patients identified as obese, producing a nonsignificant adjusted odds ratio (OR) of 0.87 (P greater than .1). Yet the rates of hemorrhage shock (OR 1.31; P = .02) and admission to the ICU (OR 1.35; P less than .02) were greater in the obese. The median length of stay of 0.35 days for obese patients was also significantly longer.

One reason for the lower rate of mortality may be more aggressive treatment. In particular, repeat endoscopy therapy was more common in those who were obese (P less than .01), suggesting, “Our treatments are working,” Dr. Abou Gergi said.

The proportion of patients with a score of 3 or greater on the Charlson comorbidity index was higher in the obese than in those not identified as obese (49% vs. 39%; P less than .01). This along with previously published evidence that obese patients take more anticoagulants, take more antiplatelets, and may face delays in endoscopy due to greater difficulty in administering sedation, were among considerations predicting a higher mortality, according to Dr. Abou Gergi.

However, there are several potential explanations for these unexpected findings. One is that mortality rates overall were low, making it difficult to show differences on this outcome. In addition, ICD-9 codes may be effective for isolating a group with obesity but not in identifying a control group without obesity.

“It is likely that not all patients who are obese received this code, so we may be seeing a population of obese patients be compared to another population that includes at least some patients who also have obesity,” explained Dr. John R. Saltzman, director of endoscopy, Brigham and Women’s Hospital, Boston. A coauthor of this study, Dr. Saltzman noted that despite a comparable rate of in-hospital mortality, most of the findings in the study argued that patients who develop upper GI bleeding have a more difficult course. He noted that this is reflected in the cost of care, which was significantly higher in those who were obese.

Although he acknowledged that he was surprised that this was “essentially a negative study,” he believes that mortality may have been “too tough” as a primary endpoint for demonstrating a difference. However, he also believes that it may be appropriate to give credit for effective treatments.

“I think that may be the key. We are just getting better at taking care of these patients,” Dr. Saltzman said.

Dr. Abou Gergi reported he has no relevant financial relationships.

HONOLULU – Obese patients who develop an upper GI bleed receive more treatment, are more likely to develop hemorrhagic shock, and are more likely to require admission to an intensive care unit than those who are not obese, but they do not have higher in-hospital mortality, according to analysis of a large national database that was presented at the annual meeting of the American College of Gastroenterology.

The significantly greater odds ratio of most major complications from upper GI bleeds in patients with obesity relative to those who are not obese was expected but so was an increased rate of in-hospital mortality, according to the first author of the study, Dr. Marwan S. Abou Gergi of Catalyst Medical Consulting, Baltimore.

Courtesy Wikimedia Commons/Med Chaos/Creative Commons 1.0

“In this study, patients with obesity received more frequent endoscopic interventions, which could explain why mortality rates were not significantly higher,” Dr. Abou Gergi reported.

In the analysis, characterized as the first study to evaluate the impact of obesity on outcomes in upper GI hemorrhage, data were drawn from the 2012 Nationwide Inpatient Sample database, which is considered to provide a representative sample of U.S. hospital experience. Drawn from more than 7 million hospitalizations, the study focused on patients 18 or over with a primary ICD-9 code for upper GI hemorrhage. The primary outcome was mortality. Secondary outcomes included interventions, ICU admissions, and length of stay.

Of the 132,545 discharges with upper GI hemorrhage, 11,220 (8.5%) were identified as obese. The in-hospital mortality overall was 1.97%, but the proportion of those who died was slightly lower among patients identified as obese, producing a nonsignificant adjusted odds ratio (OR) of 0.87 (P greater than .1). Yet the rates of hemorrhage shock (OR 1.31; P = .02) and admission to the ICU (OR 1.35; P less than .02) were greater in the obese. The median length of stay of 0.35 days for obese patients was also significantly longer.

One reason for the lower rate of mortality may be more aggressive treatment. In particular, repeat endoscopy therapy was more common in those who were obese (P less than .01), suggesting, “Our treatments are working,” Dr. Abou Gergi said.

The proportion of patients with a score of 3 or greater on the Charlson comorbidity index was higher in the obese than in those not identified as obese (49% vs. 39%; P less than .01). This along with previously published evidence that obese patients take more anticoagulants, take more antiplatelets, and may face delays in endoscopy due to greater difficulty in administering sedation, were among considerations predicting a higher mortality, according to Dr. Abou Gergi.

However, there are several potential explanations for these unexpected findings. One is that mortality rates overall were low, making it difficult to show differences on this outcome. In addition, ICD-9 codes may be effective for isolating a group with obesity but not in identifying a control group without obesity.

“It is likely that not all patients who are obese received this code, so we may be seeing a population of obese patients be compared to another population that includes at least some patients who also have obesity,” explained Dr. John R. Saltzman, director of endoscopy, Brigham and Women’s Hospital, Boston. A coauthor of this study, Dr. Saltzman noted that despite a comparable rate of in-hospital mortality, most of the findings in the study argued that patients who develop upper GI bleeding have a more difficult course. He noted that this is reflected in the cost of care, which was significantly higher in those who were obese.

Although he acknowledged that he was surprised that this was “essentially a negative study,” he believes that mortality may have been “too tough” as a primary endpoint for demonstrating a difference. However, he also believes that it may be appropriate to give credit for effective treatments.

“I think that may be the key. We are just getting better at taking care of these patients,” Dr. Saltzman said.

Dr. Abou Gergi reported he has no relevant financial relationships.

HONOLULU – Obese patients who develop an upper GI bleed receive more treatment, are more likely to develop hemorrhagic shock, and are more likely to require admission to an intensive care unit than those who are not obese, but they do not have higher in-hospital mortality, according to analysis of a large national database that was presented at the annual meeting of the American College of Gastroenterology.

The significantly greater odds ratio of most major complications from upper GI bleeds in patients with obesity relative to those who are not obese was expected but so was an increased rate of in-hospital mortality, according to the first author of the study, Dr. Marwan S. Abou Gergi of Catalyst Medical Consulting, Baltimore.

Courtesy Wikimedia Commons/Med Chaos/Creative Commons 1.0

“In this study, patients with obesity received more frequent endoscopic interventions, which could explain why mortality rates were not significantly higher,” Dr. Abou Gergi reported.

In the analysis, characterized as the first study to evaluate the impact of obesity on outcomes in upper GI hemorrhage, data were drawn from the 2012 Nationwide Inpatient Sample database, which is considered to provide a representative sample of U.S. hospital experience. Drawn from more than 7 million hospitalizations, the study focused on patients 18 or over with a primary ICD-9 code for upper GI hemorrhage. The primary outcome was mortality. Secondary outcomes included interventions, ICU admissions, and length of stay.

Of the 132,545 discharges with upper GI hemorrhage, 11,220 (8.5%) were identified as obese. The in-hospital mortality overall was 1.97%, but the proportion of those who died was slightly lower among patients identified as obese, producing a nonsignificant adjusted odds ratio (OR) of 0.87 (P greater than .1). Yet the rates of hemorrhage shock (OR 1.31; P = .02) and admission to the ICU (OR 1.35; P less than .02) were greater in the obese. The median length of stay of 0.35 days for obese patients was also significantly longer.

One reason for the lower rate of mortality may be more aggressive treatment. In particular, repeat endoscopy therapy was more common in those who were obese (P less than .01), suggesting, “Our treatments are working,” Dr. Abou Gergi said.

The proportion of patients with a score of 3 or greater on the Charlson comorbidity index was higher in the obese than in those not identified as obese (49% vs. 39%; P less than .01). This along with previously published evidence that obese patients take more anticoagulants, take more antiplatelets, and may face delays in endoscopy due to greater difficulty in administering sedation, were among considerations predicting a higher mortality, according to Dr. Abou Gergi.

However, there are several potential explanations for these unexpected findings. One is that mortality rates overall were low, making it difficult to show differences on this outcome. In addition, ICD-9 codes may be effective for isolating a group with obesity but not in identifying a control group without obesity.

“It is likely that not all patients who are obese received this code, so we may be seeing a population of obese patients be compared to another population that includes at least some patients who also have obesity,” explained Dr. John R. Saltzman, director of endoscopy, Brigham and Women’s Hospital, Boston. A coauthor of this study, Dr. Saltzman noted that despite a comparable rate of in-hospital mortality, most of the findings in the study argued that patients who develop upper GI bleeding have a more difficult course. He noted that this is reflected in the cost of care, which was significantly higher in those who were obese.

Although he acknowledged that he was surprised that this was “essentially a negative study,” he believes that mortality may have been “too tough” as a primary endpoint for demonstrating a difference. However, he also believes that it may be appropriate to give credit for effective treatments.

“I think that may be the key. We are just getting better at taking care of these patients,” Dr. Saltzman said.

Dr. Abou Gergi reported he has no relevant financial relationships.

This year’s session on esophagus/upper GI at the AGA Spring Postgraduate Course was packed with pragmatic, useful information for the evaluation of patients with upper GI disorders. The session began with a talk on the manifestations of extraesophageal reflux disease. The take-home message of this talk was that putative extraesophageal manifestations of gastroesophageal reflux disease rarely respond to high-dose therapy with PPIs (proton-pump inhibitors), in the absence of concurrent esophageal symptoms such as heartburn or regurgitation. In such situations, investigation of other etiologies of patients’ symptoms, including occult postnasal drainage or cough-variant asthma, may be more rewarding than escalating anti-acid therapy.

Dr. John E. Pandolfino, AGAF, of Northwestern University, Chicago, discussed the utilization of high-resolution manometry in the evaluation of dysphagia. A central focus of this discussion was the use of the Chicago classification of motility abnormalities in assessing these patients. In the future, it is likely that the care of these patients will be dictated by the type of abnormality the patient has in this classification scheme. Especially in the setting of achalasia, data are emerging that some subtypes of achalasia are less likely to respond to some therapies. For instance, type 3 achalasia is unlikely to respond to pneumatic balloon dilatation.

Dr. Rhonda Souza of the University of Texas Southwestern Medical Center, Dallas, taught us that a diagnosis of eosinophilic esophagitis requires an 8-week trial of PPI therapy with no resolution of the eosinophilia. Esophageal dilation is generally safe in the setting of a dominant stricture, but it can be delayed prior to medical therapy if the patient is tolerating oral intake well. Although the most commonly used therapies for EoE now involve either swallowed steroids or dietary elimination therapy, several new agents are on the horizon that may give us new treatment options.

Finally, Dr. Amitabh Chak of Case Western Reserve University, Cleveland, reviewed the care of patients with Barrett’s esophagus and low-grade dysplasia. This is an especially difficult group of patients to care for, due in part to the low reproducibility in the diagnosis of low-grade dysplasia, as well as the highly variable reported cancer outcomes in this patient population. Level 1 evidence now exists demonstrating that treatment with radiofrequency ablation decreases the incidence of cancer in patients with low-grade dysplasia, but most patients with this finding will not progress. Therefore, the field would benefit from better risk stratification of these patients.

Dr. Shaheen is professor of medicine and epidemiology and chief of the division of gastroenterology & hepatology, University of North Carolina School of Medicine, Chapel Hill. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2015.

This year’s session on esophagus/upper GI at the AGA Spring Postgraduate Course was packed with pragmatic, useful information for the evaluation of patients with upper GI disorders. The session began with a talk on the manifestations of extraesophageal reflux disease. The take-home message of this talk was that putative extraesophageal manifestations of gastroesophageal reflux disease rarely respond to high-dose therapy with PPIs (proton-pump inhibitors), in the absence of concurrent esophageal symptoms such as heartburn or regurgitation. In such situations, investigation of other etiologies of patients’ symptoms, including occult postnasal drainage or cough-variant asthma, may be more rewarding than escalating anti-acid therapy.

Dr. John E. Pandolfino, AGAF, of Northwestern University, Chicago, discussed the utilization of high-resolution manometry in the evaluation of dysphagia. A central focus of this discussion was the use of the Chicago classification of motility abnormalities in assessing these patients. In the future, it is likely that the care of these patients will be dictated by the type of abnormality the patient has in this classification scheme. Especially in the setting of achalasia, data are emerging that some subtypes of achalasia are less likely to respond to some therapies. For instance, type 3 achalasia is unlikely to respond to pneumatic balloon dilatation.

Dr. Rhonda Souza of the University of Texas Southwestern Medical Center, Dallas, taught us that a diagnosis of eosinophilic esophagitis requires an 8-week trial of PPI therapy with no resolution of the eosinophilia. Esophageal dilation is generally safe in the setting of a dominant stricture, but it can be delayed prior to medical therapy if the patient is tolerating oral intake well. Although the most commonly used therapies for EoE now involve either swallowed steroids or dietary elimination therapy, several new agents are on the horizon that may give us new treatment options.

Finally, Dr. Amitabh Chak of Case Western Reserve University, Cleveland, reviewed the care of patients with Barrett’s esophagus and low-grade dysplasia. This is an especially difficult group of patients to care for, due in part to the low reproducibility in the diagnosis of low-grade dysplasia, as well as the highly variable reported cancer outcomes in this patient population. Level 1 evidence now exists demonstrating that treatment with radiofrequency ablation decreases the incidence of cancer in patients with low-grade dysplasia, but most patients with this finding will not progress. Therefore, the field would benefit from better risk stratification of these patients.

Dr. Shaheen is professor of medicine and epidemiology and chief of the division of gastroenterology & hepatology, University of North Carolina School of Medicine, Chapel Hill. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2015.

This year’s session on esophagus/upper GI at the AGA Spring Postgraduate Course was packed with pragmatic, useful information for the evaluation of patients with upper GI disorders. The session began with a talk on the manifestations of extraesophageal reflux disease. The take-home message of this talk was that putative extraesophageal manifestations of gastroesophageal reflux disease rarely respond to high-dose therapy with PPIs (proton-pump inhibitors), in the absence of concurrent esophageal symptoms such as heartburn or regurgitation. In such situations, investigation of other etiologies of patients’ symptoms, including occult postnasal drainage or cough-variant asthma, may be more rewarding than escalating anti-acid therapy.

Dr. John E. Pandolfino, AGAF, of Northwestern University, Chicago, discussed the utilization of high-resolution manometry in the evaluation of dysphagia. A central focus of this discussion was the use of the Chicago classification of motility abnormalities in assessing these patients. In the future, it is likely that the care of these patients will be dictated by the type of abnormality the patient has in this classification scheme. Especially in the setting of achalasia, data are emerging that some subtypes of achalasia are less likely to respond to some therapies. For instance, type 3 achalasia is unlikely to respond to pneumatic balloon dilatation.

Dr. Rhonda Souza of the University of Texas Southwestern Medical Center, Dallas, taught us that a diagnosis of eosinophilic esophagitis requires an 8-week trial of PPI therapy with no resolution of the eosinophilia. Esophageal dilation is generally safe in the setting of a dominant stricture, but it can be delayed prior to medical therapy if the patient is tolerating oral intake well. Although the most commonly used therapies for EoE now involve either swallowed steroids or dietary elimination therapy, several new agents are on the horizon that may give us new treatment options.

Finally, Dr. Amitabh Chak of Case Western Reserve University, Cleveland, reviewed the care of patients with Barrett’s esophagus and low-grade dysplasia. This is an especially difficult group of patients to care for, due in part to the low reproducibility in the diagnosis of low-grade dysplasia, as well as the highly variable reported cancer outcomes in this patient population. Level 1 evidence now exists demonstrating that treatment with radiofrequency ablation decreases the incidence of cancer in patients with low-grade dysplasia, but most patients with this finding will not progress. Therefore, the field would benefit from better risk stratification of these patients.

Dr. Shaheen is professor of medicine and epidemiology and chief of the division of gastroenterology & hepatology, University of North Carolina School of Medicine, Chapel Hill. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2015.

LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.

Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.

In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.

The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.

“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.

The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.

More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.

General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.

Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).

There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).

Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.

The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).

“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”

Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.

The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.

The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.

LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.

Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.

In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.

The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.

“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.

The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.

More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.

General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.

Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).

There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).

Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.

The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).

“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”

Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.

The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.

The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.

LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.

Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.

In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.

The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.

“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.

The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.

More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.

General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.

Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).

There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).

Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.

The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).

“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”

Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.

The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.

The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.

Only half of Helicobacter pylori strains were pansusceptible, and almost one in three was resistant to at least one antibiotic, according to a single-center study of U.S. veterans published in Clinical Gastroenterology and Hepatology.

The analysis is the first published report of H. pylori resistance in more than a decade, said Dr. Seiji Shiota at the Michael E. DeBakey Veterans Affairs Medical Center and the Baylor College of Medicine, Houston, and his associates. “Clarithromycin, metronidazole, and levofloxacin resistances were all high among untreated patients, suggesting that they all should be avoided as components of empiric triple therapy [consisting of a] proton pump inhibitor, amoxicillin, plus a third antibiotic,” said the researchers. “The four-drug concomitant therapy and bismuth quadruple therapy, or antibiotic susceptibility–guided therapy, are likely be the best strategies locally and are recommended for previously untreated patients with H. pylori infection.”

© NDDIC.NIH.gov

The study assessed 656 gastric biopsies randomly selected from a cohort of 1,559 patients who underwent esophagogastroduodenoscopy at the Houston VA Medical Center between 2009 and 2013. About 90% of patients were male, and patients ranged in age from 40 to 79 years old, with an average age of 60 years. The researchers cultured tissue samples and used the E test to assess minimum inhibitory concentrations for amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline. (Clin Gastroenterol Hepatol. 2015 Feb 11. pii: S1542-3565(15)00122-6).

A total of 135 (20.6%) of the biopsies cultured H. pylori, of which half (65 strains) were susceptible to all five antibiotics tested, 31% were resistant to levofloxacin (95% confidence interval, 23%-39%), 20% were resistant to metronidazole (95% CI, 13%-27%), 16% were resistant to clarithromycin (95% CI, 10%-23%), 0.8% were resistant to tetracycline (95% CI, 0%-2%), and none were resistant to amoxicillin, said the researchers. The extent of levofloxacin resistance was a “new and concerning finding” that was linked in the multivariable analysis with past fluoroquinolone treatment, reflecting the rising use of fluoroquinolones in community practice, they said. “Levofloxacin has been recommended as a rescue drug to eradicate H. pylori in patients who fail first-line therapy,” they added. “Locally, it would seem to be a poor choice on the basis of the high resistance rate (31.9%), which is higher than the 10% limit suggested as a cutoff for use of fluoroquinolone-containing triple therapy for H. pylori.”

Clarithromycin resistance also rose during the study period, probably because of the rising use of macrolides in respiratory and otorhinolaryngology, the investigators noted. Patients who had been treated before for helicobacteriosis were significantly more likely to have clarithromycin-resistant H. pylori infections even after accounting for demographic factors, smoking status, gastroesophageal reflux disease, and past use of macrolides and fluoroquinolones, they said. Based on that result, patients with a history of prior helicobacteriosis should not receive clarithromycin as part of triple therapy, they emphasized.

Resistance to metronidazole also remained high, but only 1.8% of isolates were resistant to both metronidazole and clarithromycin, making combination therapy with a proton pump inhibitor, clarithromycin, metronidazole, and amoxicillin “an excellent choice as an empiric therapy,” added Dr. Shiota and his associates. Furthermore, the study might have overestimated the rate of metronidazole resistance because the E test yielded significantly higher minimum inhibitory concentration values than did agar dilution, they noted. The study cohort also was demographically dissimilar to that of the United States and might have reflected selection bias, because patients with a history of helicobacteriosis would be more likely to be referred for endoscopy, they said.

The National Institutes of Health and the Veterans Affairs Health Services Research & Development Center for Innovations in Quality, Effectiveness, and Safety supported the study. The researchers reported having no conflicts of interest.

Only half of Helicobacter pylori strains were pansusceptible, and almost one in three was resistant to at least one antibiotic, according to a single-center study of U.S. veterans published in Clinical Gastroenterology and Hepatology.

The analysis is the first published report of H. pylori resistance in more than a decade, said Dr. Seiji Shiota at the Michael E. DeBakey Veterans Affairs Medical Center and the Baylor College of Medicine, Houston, and his associates. “Clarithromycin, metronidazole, and levofloxacin resistances were all high among untreated patients, suggesting that they all should be avoided as components of empiric triple therapy [consisting of a] proton pump inhibitor, amoxicillin, plus a third antibiotic,” said the researchers. “The four-drug concomitant therapy and bismuth quadruple therapy, or antibiotic susceptibility–guided therapy, are likely be the best strategies locally and are recommended for previously untreated patients with H. pylori infection.”

© NDDIC.NIH.gov

The study assessed 656 gastric biopsies randomly selected from a cohort of 1,559 patients who underwent esophagogastroduodenoscopy at the Houston VA Medical Center between 2009 and 2013. About 90% of patients were male, and patients ranged in age from 40 to 79 years old, with an average age of 60 years. The researchers cultured tissue samples and used the E test to assess minimum inhibitory concentrations for amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline. (Clin Gastroenterol Hepatol. 2015 Feb 11. pii: S1542-3565(15)00122-6).

A total of 135 (20.6%) of the biopsies cultured H. pylori, of which half (65 strains) were susceptible to all five antibiotics tested, 31% were resistant to levofloxacin (95% confidence interval, 23%-39%), 20% were resistant to metronidazole (95% CI, 13%-27%), 16% were resistant to clarithromycin (95% CI, 10%-23%), 0.8% were resistant to tetracycline (95% CI, 0%-2%), and none were resistant to amoxicillin, said the researchers. The extent of levofloxacin resistance was a “new and concerning finding” that was linked in the multivariable analysis with past fluoroquinolone treatment, reflecting the rising use of fluoroquinolones in community practice, they said. “Levofloxacin has been recommended as a rescue drug to eradicate H. pylori in patients who fail first-line therapy,” they added. “Locally, it would seem to be a poor choice on the basis of the high resistance rate (31.9%), which is higher than the 10% limit suggested as a cutoff for use of fluoroquinolone-containing triple therapy for H. pylori.”

Clarithromycin resistance also rose during the study period, probably because of the rising use of macrolides in respiratory and otorhinolaryngology, the investigators noted. Patients who had been treated before for helicobacteriosis were significantly more likely to have clarithromycin-resistant H. pylori infections even after accounting for demographic factors, smoking status, gastroesophageal reflux disease, and past use of macrolides and fluoroquinolones, they said. Based on that result, patients with a history of prior helicobacteriosis should not receive clarithromycin as part of triple therapy, they emphasized.

Resistance to metronidazole also remained high, but only 1.8% of isolates were resistant to both metronidazole and clarithromycin, making combination therapy with a proton pump inhibitor, clarithromycin, metronidazole, and amoxicillin “an excellent choice as an empiric therapy,” added Dr. Shiota and his associates. Furthermore, the study might have overestimated the rate of metronidazole resistance because the E test yielded significantly higher minimum inhibitory concentration values than did agar dilution, they noted. The study cohort also was demographically dissimilar to that of the United States and might have reflected selection bias, because patients with a history of helicobacteriosis would be more likely to be referred for endoscopy, they said.

The National Institutes of Health and the Veterans Affairs Health Services Research & Development Center for Innovations in Quality, Effectiveness, and Safety supported the study. The researchers reported having no conflicts of interest.

Only half of Helicobacter pylori strains were pansusceptible, and almost one in three was resistant to at least one antibiotic, according to a single-center study of U.S. veterans published in Clinical Gastroenterology and Hepatology.

The analysis is the first published report of H. pylori resistance in more than a decade, said Dr. Seiji Shiota at the Michael E. DeBakey Veterans Affairs Medical Center and the Baylor College of Medicine, Houston, and his associates. “Clarithromycin, metronidazole, and levofloxacin resistances were all high among untreated patients, suggesting that they all should be avoided as components of empiric triple therapy [consisting of a] proton pump inhibitor, amoxicillin, plus a third antibiotic,” said the researchers. “The four-drug concomitant therapy and bismuth quadruple therapy, or antibiotic susceptibility–guided therapy, are likely be the best strategies locally and are recommended for previously untreated patients with H. pylori infection.”

© NDDIC.NIH.gov

The study assessed 656 gastric biopsies randomly selected from a cohort of 1,559 patients who underwent esophagogastroduodenoscopy at the Houston VA Medical Center between 2009 and 2013. About 90% of patients were male, and patients ranged in age from 40 to 79 years old, with an average age of 60 years. The researchers cultured tissue samples and used the E test to assess minimum inhibitory concentrations for amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline. (Clin Gastroenterol Hepatol. 2015 Feb 11. pii: S1542-3565(15)00122-6).

A total of 135 (20.6%) of the biopsies cultured H. pylori, of which half (65 strains) were susceptible to all five antibiotics tested, 31% were resistant to levofloxacin (95% confidence interval, 23%-39%), 20% were resistant to metronidazole (95% CI, 13%-27%), 16% were resistant to clarithromycin (95% CI, 10%-23%), 0.8% were resistant to tetracycline (95% CI, 0%-2%), and none were resistant to amoxicillin, said the researchers. The extent of levofloxacin resistance was a “new and concerning finding” that was linked in the multivariable analysis with past fluoroquinolone treatment, reflecting the rising use of fluoroquinolones in community practice, they said. “Levofloxacin has been recommended as a rescue drug to eradicate H. pylori in patients who fail first-line therapy,” they added. “Locally, it would seem to be a poor choice on the basis of the high resistance rate (31.9%), which is higher than the 10% limit suggested as a cutoff for use of fluoroquinolone-containing triple therapy for H. pylori.”

Clarithromycin resistance also rose during the study period, probably because of the rising use of macrolides in respiratory and otorhinolaryngology, the investigators noted. Patients who had been treated before for helicobacteriosis were significantly more likely to have clarithromycin-resistant H. pylori infections even after accounting for demographic factors, smoking status, gastroesophageal reflux disease, and past use of macrolides and fluoroquinolones, they said. Based on that result, patients with a history of prior helicobacteriosis should not receive clarithromycin as part of triple therapy, they emphasized.

Resistance to metronidazole also remained high, but only 1.8% of isolates were resistant to both metronidazole and clarithromycin, making combination therapy with a proton pump inhibitor, clarithromycin, metronidazole, and amoxicillin “an excellent choice as an empiric therapy,” added Dr. Shiota and his associates. Furthermore, the study might have overestimated the rate of metronidazole resistance because the E test yielded significantly higher minimum inhibitory concentration values than did agar dilution, they noted. The study cohort also was demographically dissimilar to that of the United States and might have reflected selection bias, because patients with a history of helicobacteriosis would be more likely to be referred for endoscopy, they said.

The National Institutes of Health and the Veterans Affairs Health Services Research & Development Center for Innovations in Quality, Effectiveness, and Safety supported the study. The researchers reported having no conflicts of interest.

Patients with Barrett’s esophagus have about a 0.2% annual chance of developing esophageal adenocarcinoma in the 5 years after initial diagnosis, but the likelihood then rises so that about 9% of all patients will develop cancer by 20 years out, according to a study in the September issue of Gastroenterology.

The modeled rates of progression for the early years after diagnosis are substantially lower than are those reported by prospective studies, which involve more intensive surveillance and therefore suffer from detection bias, said Dr. Sonja Kroep of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates. “Clinicians informing their patients about their cancer risk can best use this clinical progression rate, which is not influenced by surveillance-detected cancers,” they wrote.

Past analyses have yielded varying results for the rate at which Barrett’s esophagus with low-grade dysplasia progresses to high-grade dysplasia and esophageal carcinoma. For their study, Dr. Kroep and her associates calibrated a model based on the annual rate of 0.18% reported by population-level studies, and used it to simulate prospective studies and to predict results from both population-based and prospective studies for various follow-up periods (Gastroenterology 2015 Apr 29. pii: S0016-5085(15)00601-0).

For the first 5 years of follow-up, the model predicted a 0.19% annual rate of transformation to esophageal adenocarcinoma for population-based studies and a 0.36% annual rate for prospective studies, the researchers reported. At 20 years, these rates rose to 0.63% and 0.65% annually, for a cumulative incidence rate of 9.1% to 9.5%. Between the 5-year and 20-year thresholds, the gap between rates of progression for the two types of studies narrowed from 91% to 5%. Taken together, the findings suggest that for the first 5 years after a diagnosis of Barrett’s esophagus, rates of progression to esophageal adenocarcinoma reflect those from population-level studies instead of surveillance-based prospective studies, the investigators said. “Clinicians should use this information to explain to patients their short-term and long-term risks if no action is taken, and then discuss the risks and benefits of surveillance,” they added.

In a separate retrospective study, radiofrequency ablation of low-grade esophageal dysplasia was linked to substantially lower rates of progression compared with watchful waiting in the form of endoscopic surveillance, said Dr. Aaron Small of the University of Pennsylvania, Philadelphia, and his associates. Their study included 125 patients with Barrett’s esophagus and low-grade dysplasia who underwent surveillance only, and 45 patients who underwent radiofrequency ablation at three university medical centers.

Over median follow-up periods of more than 2 years, the risk of progression with radiofrequency ablation was significantly lower than with endoscopic surveillance only, even after the researchers controlled for year of diagnosis (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008-0.48; P = .008). The ablation group also had fewer visible macroscopic lesions, although the difference was not significant. “We estimate that for every three patients treated with radiofrequency ablation, one additional patient with low-grade dysplasia will avoid progression to high-grade dysplasia or esophageal adenocarcinoma within 3 years,” the researchers wrote. “Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for low-grade dysplasia” (Gastroenterology 2015 Apr 24. pii: S0016-5085(15)00569-7).

The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest. The study by Dr. Small and his associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest, but seven coauthors reported ties with a number of pharmaceutical companies.

Patients with Barrett’s esophagus have about a 0.2% annual chance of developing esophageal adenocarcinoma in the 5 years after initial diagnosis, but the likelihood then rises so that about 9% of all patients will develop cancer by 20 years out, according to a study in the September issue of Gastroenterology.

The modeled rates of progression for the early years after diagnosis are substantially lower than are those reported by prospective studies, which involve more intensive surveillance and therefore suffer from detection bias, said Dr. Sonja Kroep of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates. “Clinicians informing their patients about their cancer risk can best use this clinical progression rate, which is not influenced by surveillance-detected cancers,” they wrote.

Past analyses have yielded varying results for the rate at which Barrett’s esophagus with low-grade dysplasia progresses to high-grade dysplasia and esophageal carcinoma. For their study, Dr. Kroep and her associates calibrated a model based on the annual rate of 0.18% reported by population-level studies, and used it to simulate prospective studies and to predict results from both population-based and prospective studies for various follow-up periods (Gastroenterology 2015 Apr 29. pii: S0016-5085(15)00601-0).

For the first 5 years of follow-up, the model predicted a 0.19% annual rate of transformation to esophageal adenocarcinoma for population-based studies and a 0.36% annual rate for prospective studies, the researchers reported. At 20 years, these rates rose to 0.63% and 0.65% annually, for a cumulative incidence rate of 9.1% to 9.5%. Between the 5-year and 20-year thresholds, the gap between rates of progression for the two types of studies narrowed from 91% to 5%. Taken together, the findings suggest that for the first 5 years after a diagnosis of Barrett’s esophagus, rates of progression to esophageal adenocarcinoma reflect those from population-level studies instead of surveillance-based prospective studies, the investigators said. “Clinicians should use this information to explain to patients their short-term and long-term risks if no action is taken, and then discuss the risks and benefits of surveillance,” they added.

In a separate retrospective study, radiofrequency ablation of low-grade esophageal dysplasia was linked to substantially lower rates of progression compared with watchful waiting in the form of endoscopic surveillance, said Dr. Aaron Small of the University of Pennsylvania, Philadelphia, and his associates. Their study included 125 patients with Barrett’s esophagus and low-grade dysplasia who underwent surveillance only, and 45 patients who underwent radiofrequency ablation at three university medical centers.

Over median follow-up periods of more than 2 years, the risk of progression with radiofrequency ablation was significantly lower than with endoscopic surveillance only, even after the researchers controlled for year of diagnosis (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008-0.48; P = .008). The ablation group also had fewer visible macroscopic lesions, although the difference was not significant. “We estimate that for every three patients treated with radiofrequency ablation, one additional patient with low-grade dysplasia will avoid progression to high-grade dysplasia or esophageal adenocarcinoma within 3 years,” the researchers wrote. “Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for low-grade dysplasia” (Gastroenterology 2015 Apr 24. pii: S0016-5085(15)00569-7).

The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest. The study by Dr. Small and his associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest, but seven coauthors reported ties with a number of pharmaceutical companies.

Patients with Barrett’s esophagus have about a 0.2% annual chance of developing esophageal adenocarcinoma in the 5 years after initial diagnosis, but the likelihood then rises so that about 9% of all patients will develop cancer by 20 years out, according to a study in the September issue of Gastroenterology.

The modeled rates of progression for the early years after diagnosis are substantially lower than are those reported by prospective studies, which involve more intensive surveillance and therefore suffer from detection bias, said Dr. Sonja Kroep of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates. “Clinicians informing their patients about their cancer risk can best use this clinical progression rate, which is not influenced by surveillance-detected cancers,” they wrote.

Past analyses have yielded varying results for the rate at which Barrett’s esophagus with low-grade dysplasia progresses to high-grade dysplasia and esophageal carcinoma. For their study, Dr. Kroep and her associates calibrated a model based on the annual rate of 0.18% reported by population-level studies, and used it to simulate prospective studies and to predict results from both population-based and prospective studies for various follow-up periods (Gastroenterology 2015 Apr 29. pii: S0016-5085(15)00601-0).

For the first 5 years of follow-up, the model predicted a 0.19% annual rate of transformation to esophageal adenocarcinoma for population-based studies and a 0.36% annual rate for prospective studies, the researchers reported. At 20 years, these rates rose to 0.63% and 0.65% annually, for a cumulative incidence rate of 9.1% to 9.5%. Between the 5-year and 20-year thresholds, the gap between rates of progression for the two types of studies narrowed from 91% to 5%. Taken together, the findings suggest that for the first 5 years after a diagnosis of Barrett’s esophagus, rates of progression to esophageal adenocarcinoma reflect those from population-level studies instead of surveillance-based prospective studies, the investigators said. “Clinicians should use this information to explain to patients their short-term and long-term risks if no action is taken, and then discuss the risks and benefits of surveillance,” they added.

In a separate retrospective study, radiofrequency ablation of low-grade esophageal dysplasia was linked to substantially lower rates of progression compared with watchful waiting in the form of endoscopic surveillance, said Dr. Aaron Small of the University of Pennsylvania, Philadelphia, and his associates. Their study included 125 patients with Barrett’s esophagus and low-grade dysplasia who underwent surveillance only, and 45 patients who underwent radiofrequency ablation at three university medical centers.

Over median follow-up periods of more than 2 years, the risk of progression with radiofrequency ablation was significantly lower than with endoscopic surveillance only, even after the researchers controlled for year of diagnosis (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008-0.48; P = .008). The ablation group also had fewer visible macroscopic lesions, although the difference was not significant. “We estimate that for every three patients treated with radiofrequency ablation, one additional patient with low-grade dysplasia will avoid progression to high-grade dysplasia or esophageal adenocarcinoma within 3 years,” the researchers wrote. “Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for low-grade dysplasia” (Gastroenterology 2015 Apr 24. pii: S0016-5085(15)00569-7).

The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest. The study by Dr. Small and his associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest, but seven coauthors reported ties with a number of pharmaceutical companies.

WASHINGTON – Five-year follow-up data on the magnetic device approved for treating gastroesophageal reflux disease confirm its long-term safety and efficacy, Dr. Robert A. Ganz reported at the annual Digestive Disease Week.

Five years after device implantation, the proportion of patients experiencing moderate to severe regurgitation had dropped to about 1%, from almost 60% at baseline, and two-thirds of patients were not taking any proton pump inhibitors (PPIs), said Dr. Ganz, chief of gastroenterology at Abbott Northwestern Hospital, Minneapolis, and one of the study investigators. These were among the results of the study that evaluated the device, the LINX Reflux Management System. The device was approved by the Food and Drug Administration FDA) in 2012 and is for the treatment of people with GERD as defined by abnormal pH testing, who continue to have chronic GERD symptoms that persist despite maximum medical therapy for the treatment of reflux.

“Magnetic sphincter augmentation should be considered first-line surgical therapy for those with gastroesophageal reflux disease, based on the results of this study,” he said.

The 2-year results of the prospective, multicenter study were the basis of the FDA approval of the device, described by the manufacturer, Torax Medical, as a “small implant [composed] of interlinked titanium beads with magnetic cores,” implanted during standard laparoscopy. The magnetic attraction between the beads augments the existing esophageal sphincter’s barrier function to prevent reflux,” according to the company.

The study enrolled 100 patients with reflux disease with a median age of 53 years, who had experienced typical heartburn for at least 6 months with or without regurgitation and were taking PPIs daily for at least 3 months (median use 5 years). Patients had GERD for a median of 10 years (range: 1-40 years). People who had any type of previous gastric or esophageal surgery, Barrett’s esophagus, a hiatal hernia greater than 3 cm, a body mass index over 35 kg/m², or grade C or D esophagitis were excluded.

The device was implanted in all patients, who served as their own controls; 85 patients were followed through 5 years (6 were lost to follow-up, the device was explanted in 6 patients, 2 patients did not consent to extended follow-up, and 1 patient died of an unrelated cancer). The median procedure time was 36 minutes with a range of 7-125 minutes); all procedures were successfully completed with no intraoperative complications and all patients were discharged within 24 hours on an unrestricted diet.

The median total Gastroesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) score at baseline was 27 points among those not on PPIs and 11 points on PPIs, dropping to 4 points at 5 years off PPIs. At baseline, 95% of patients expressed dissatisfaction related to reflux, which dropped to 7% at year 5. Moderate to severe heartburn was reported by 89% at baseline, dropping to about 12% at year 5. The proportion of patients experiencing moderate to severe regurgitation dropped from 57% at baseline to about 1% at 5 years, Dr. Ganz said.

At baseline, 100% were taking PPIs every day, compared with 15% at 5 years. (At 5 years, 75% had discontinued PPIs, and about 9% reported PRN use only). Grade A and B esophagitis decreased from 40% at baseline to 16% at 5 years, at which point most cases were grade A, and there were no patients with grade C or D esophagitis, he said. In addition, at 5 years, 100% of patients “reported the ability to belch, and those needing to vomit – about 16% – reported the ability to vomit,” demonstrating that normal physiology was preserved with the device.

At 5 years, there were no device erosions or migrations, or any significant adverse events other than dysphagia, which “was typically mild and not associated with weight loss and tended to resolve over time,” from about 70% in the first few weeks after surgery to 11% at 1 year and 7% at 5 years, Dr. Ganz said.

In seven cases, the device was removed laparoscopically, with no complications and gastric anatomy was preserved for future treatments. All removals were elective. The device was removed in four patients because of dysphagia, which completely resolved in those patients. One patient had the device removed because of vomiting of unknown cause that persisted after removal. Another two patients who “had the device removed for disease management” continued to experience reflux and had “uneventful” Nissen fundoplication,” he said.

“Five years after magnetic augmentation, we have demonstrated objective evidence of reduction in acid exposure and in the majority of patients, normalized pH [and] we demonstrated significant and durable improvement in all group parameters measured, with preservation of fundic anatomy and normal physiology, with the ability to belch and vomit,” Dr. Ganz concluded. The results also show that the “procedure is reproducible, safe and reversible if necessary,” he added, noting that one of the limitations of the study was that subjects served as their own controls. During the discussion period, he was asked about hiatal hernia repairs, an apparent trend to “decay” from years 1 to 5 in some parameters measured, and dysphagia after the procedure.

About 40% of the patients in the study had a hiatal hernia, and about one-third of these patients had a hernia repair. A subgroup analysis of the data is being performed to evaluate the impact of hernia repair, Dr. Ganz said.

PPI use increased from 8% in year 4, to 15% in year 5. The reason for this s difficult to determine but “even though there is a bit of a decay, patients are still quite satisfied at 5 years,” Dr. Ganz remarked, also referring to the marked impact on regurgitation. Many U.S. patients use PPIs for reasons other than reflux, and studies show that many patients are on PPIs after the Nissen procedure in the absence of pathologic pH scores, he pointed out.

Compared with the type of dysphagia patients experience after the Nissen procedure, which is immediate and improves with time, Dr. Ganz said that the dysphagia associated with the device “seemed to peak around 2 weeks and then it slowly improved with time, so this may be more of a scar tissue–associated dysphagia than an edema dysphagia, but … it does improve with time.

Three-year results of the study were published in 2013 (N. Engl. J. Med. 2013;368:719-72), Dr. Ganz was the lead author.

The study was funded by Torax Medical. Dr. Ganz had no disclosures related to the topic of this presentation.

*This story was updated 7/9/2015.

[email protected]

WASHINGTON – Five-year follow-up data on the magnetic device approved for treating gastroesophageal reflux disease confirm its long-term safety and efficacy, Dr. Robert A. Ganz reported at the annual Digestive Disease Week.

Five years after device implantation, the proportion of patients experiencing moderate to severe regurgitation had dropped to about 1%, from almost 60% at baseline, and two-thirds of patients were not taking any proton pump inhibitors (PPIs), said Dr. Ganz, chief of gastroenterology at Abbott Northwestern Hospital, Minneapolis, and one of the study investigators. These were among the results of the study that evaluated the device, the LINX Reflux Management System. The device was approved by the Food and Drug Administration FDA) in 2012 and is for the treatment of people with GERD as defined by abnormal pH testing, who continue to have chronic GERD symptoms that persist despite maximum medical therapy for the treatment of reflux.

“Magnetic sphincter augmentation should be considered first-line surgical therapy for those with gastroesophageal reflux disease, based on the results of this study,” he said.

The 2-year results of the prospective, multicenter study were the basis of the FDA approval of the device, described by the manufacturer, Torax Medical, as a “small implant [composed] of interlinked titanium beads with magnetic cores,” implanted during standard laparoscopy. The magnetic attraction between the beads augments the existing esophageal sphincter’s barrier function to prevent reflux,” according to the company.

The study enrolled 100 patients with reflux disease with a median age of 53 years, who had experienced typical heartburn for at least 6 months with or without regurgitation and were taking PPIs daily for at least 3 months (median use 5 years). Patients had GERD for a median of 10 years (range: 1-40 years). People who had any type of previous gastric or esophageal surgery, Barrett’s esophagus, a hiatal hernia greater than 3 cm, a body mass index over 35 kg/m², or grade C or D esophagitis were excluded.

The device was implanted in all patients, who served as their own controls; 85 patients were followed through 5 years (6 were lost to follow-up, the device was explanted in 6 patients, 2 patients did not consent to extended follow-up, and 1 patient died of an unrelated cancer). The median procedure time was 36 minutes with a range of 7-125 minutes); all procedures were successfully completed with no intraoperative complications and all patients were discharged within 24 hours on an unrestricted diet.

The median total Gastroesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) score at baseline was 27 points among those not on PPIs and 11 points on PPIs, dropping to 4 points at 5 years off PPIs. At baseline, 95% of patients expressed dissatisfaction related to reflux, which dropped to 7% at year 5. Moderate to severe heartburn was reported by 89% at baseline, dropping to about 12% at year 5. The proportion of patients experiencing moderate to severe regurgitation dropped from 57% at baseline to about 1% at 5 years, Dr. Ganz said.

At baseline, 100% were taking PPIs every day, compared with 15% at 5 years. (At 5 years, 75% had discontinued PPIs, and about 9% reported PRN use only). Grade A and B esophagitis decreased from 40% at baseline to 16% at 5 years, at which point most cases were grade A, and there were no patients with grade C or D esophagitis, he said. In addition, at 5 years, 100% of patients “reported the ability to belch, and those needing to vomit – about 16% – reported the ability to vomit,” demonstrating that normal physiology was preserved with the device.

At 5 years, there were no device erosions or migrations, or any significant adverse events other than dysphagia, which “was typically mild and not associated with weight loss and tended to resolve over time,” from about 70% in the first few weeks after surgery to 11% at 1 year and 7% at 5 years, Dr. Ganz said.

In seven cases, the device was removed laparoscopically, with no complications and gastric anatomy was preserved for future treatments. All removals were elective. The device was removed in four patients because of dysphagia, which completely resolved in those patients. One patient had the device removed because of vomiting of unknown cause that persisted after removal. Another two patients who “had the device removed for disease management” continued to experience reflux and had “uneventful” Nissen fundoplication,” he said.

“Five years after magnetic augmentation, we have demonstrated objective evidence of reduction in acid exposure and in the majority of patients, normalized pH [and] we demonstrated significant and durable improvement in all group parameters measured, with preservation of fundic anatomy and normal physiology, with the ability to belch and vomit,” Dr. Ganz concluded. The results also show that the “procedure is reproducible, safe and reversible if necessary,” he added, noting that one of the limitations of the study was that subjects served as their own controls. During the discussion period, he was asked about hiatal hernia repairs, an apparent trend to “decay” from years 1 to 5 in some parameters measured, and dysphagia after the procedure.

About 40% of the patients in the study had a hiatal hernia, and about one-third of these patients had a hernia repair. A subgroup analysis of the data is being performed to evaluate the impact of hernia repair, Dr. Ganz said.

PPI use increased from 8% in year 4, to 15% in year 5. The reason for this s difficult to determine but “even though there is a bit of a decay, patients are still quite satisfied at 5 years,” Dr. Ganz remarked, also referring to the marked impact on regurgitation. Many U.S. patients use PPIs for reasons other than reflux, and studies show that many patients are on PPIs after the Nissen procedure in the absence of pathologic pH scores, he pointed out.

Compared with the type of dysphagia patients experience after the Nissen procedure, which is immediate and improves with time, Dr. Ganz said that the dysphagia associated with the device “seemed to peak around 2 weeks and then it slowly improved with time, so this may be more of a scar tissue–associated dysphagia than an edema dysphagia, but … it does improve with time.

Three-year results of the study were published in 2013 (N. Engl. J. Med. 2013;368:719-72), Dr. Ganz was the lead author.

The study was funded by Torax Medical. Dr. Ganz had no disclosures related to the topic of this presentation.

*This story was updated 7/9/2015.

[email protected]

WASHINGTON – Five-year follow-up data on the magnetic device approved for treating gastroesophageal reflux disease confirm its long-term safety and efficacy, Dr. Robert A. Ganz reported at the annual Digestive Disease Week.

Five years after device implantation, the proportion of patients experiencing moderate to severe regurgitation had dropped to about 1%, from almost 60% at baseline, and two-thirds of patients were not taking any proton pump inhibitors (PPIs), said Dr. Ganz, chief of gastroenterology at Abbott Northwestern Hospital, Minneapolis, and one of the study investigators. These were among the results of the study that evaluated the device, the LINX Reflux Management System. The device was approved by the Food and Drug Administration FDA) in 2012 and is for the treatment of people with GERD as defined by abnormal pH testing, who continue to have chronic GERD symptoms that persist despite maximum medical therapy for the treatment of reflux.

“Magnetic sphincter augmentation should be considered first-line surgical therapy for those with gastroesophageal reflux disease, based on the results of this study,” he said.

The 2-year results of the prospective, multicenter study were the basis of the FDA approval of the device, described by the manufacturer, Torax Medical, as a “small implant [composed] of interlinked titanium beads with magnetic cores,” implanted during standard laparoscopy. The magnetic attraction between the beads augments the existing esophageal sphincter’s barrier function to prevent reflux,” according to the company.

The study enrolled 100 patients with reflux disease with a median age of 53 years, who had experienced typical heartburn for at least 6 months with or without regurgitation and were taking PPIs daily for at least 3 months (median use 5 years). Patients had GERD for a median of 10 years (range: 1-40 years). People who had any type of previous gastric or esophageal surgery, Barrett’s esophagus, a hiatal hernia greater than 3 cm, a body mass index over 35 kg/m², or grade C or D esophagitis were excluded.

The device was implanted in all patients, who served as their own controls; 85 patients were followed through 5 years (6 were lost to follow-up, the device was explanted in 6 patients, 2 patients did not consent to extended follow-up, and 1 patient died of an unrelated cancer). The median procedure time was 36 minutes with a range of 7-125 minutes); all procedures were successfully completed with no intraoperative complications and all patients were discharged within 24 hours on an unrestricted diet.

The median total Gastroesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) score at baseline was 27 points among those not on PPIs and 11 points on PPIs, dropping to 4 points at 5 years off PPIs. At baseline, 95% of patients expressed dissatisfaction related to reflux, which dropped to 7% at year 5. Moderate to severe heartburn was reported by 89% at baseline, dropping to about 12% at year 5. The proportion of patients experiencing moderate to severe regurgitation dropped from 57% at baseline to about 1% at 5 years, Dr. Ganz said.

At baseline, 100% were taking PPIs every day, compared with 15% at 5 years. (At 5 years, 75% had discontinued PPIs, and about 9% reported PRN use only). Grade A and B esophagitis decreased from 40% at baseline to 16% at 5 years, at which point most cases were grade A, and there were no patients with grade C or D esophagitis, he said. In addition, at 5 years, 100% of patients “reported the ability to belch, and those needing to vomit – about 16% – reported the ability to vomit,” demonstrating that normal physiology was preserved with the device.

At 5 years, there were no device erosions or migrations, or any significant adverse events other than dysphagia, which “was typically mild and not associated with weight loss and tended to resolve over time,” from about 70% in the first few weeks after surgery to 11% at 1 year and 7% at 5 years, Dr. Ganz said.

In seven cases, the device was removed laparoscopically, with no complications and gastric anatomy was preserved for future treatments. All removals were elective. The device was removed in four patients because of dysphagia, which completely resolved in those patients. One patient had the device removed because of vomiting of unknown cause that persisted after removal. Another two patients who “had the device removed for disease management” continued to experience reflux and had “uneventful” Nissen fundoplication,” he said.

“Five years after magnetic augmentation, we have demonstrated objective evidence of reduction in acid exposure and in the majority of patients, normalized pH [and] we demonstrated significant and durable improvement in all group parameters measured, with preservation of fundic anatomy and normal physiology, with the ability to belch and vomit,” Dr. Ganz concluded. The results also show that the “procedure is reproducible, safe and reversible if necessary,” he added, noting that one of the limitations of the study was that subjects served as their own controls. During the discussion period, he was asked about hiatal hernia repairs, an apparent trend to “decay” from years 1 to 5 in some parameters measured, and dysphagia after the procedure.

About 40% of the patients in the study had a hiatal hernia, and about one-third of these patients had a hernia repair. A subgroup analysis of the data is being performed to evaluate the impact of hernia repair, Dr. Ganz said.

PPI use increased from 8% in year 4, to 15% in year 5. The reason for this s difficult to determine but “even though there is a bit of a decay, patients are still quite satisfied at 5 years,” Dr. Ganz remarked, also referring to the marked impact on regurgitation. Many U.S. patients use PPIs for reasons other than reflux, and studies show that many patients are on PPIs after the Nissen procedure in the absence of pathologic pH scores, he pointed out.

Compared with the type of dysphagia patients experience after the Nissen procedure, which is immediate and improves with time, Dr. Ganz said that the dysphagia associated with the device “seemed to peak around 2 weeks and then it slowly improved with time, so this may be more of a scar tissue–associated dysphagia than an edema dysphagia, but … it does improve with time.

Three-year results of the study were published in 2013 (N. Engl. J. Med. 2013;368:719-72), Dr. Ganz was the lead author.

The study was funded by Torax Medical. Dr. Ganz had no disclosures related to the topic of this presentation.

*This story was updated 7/9/2015.

[email protected]

WASHINGTON – Two weeks of antibiotic therapy with rifaximin provided relief from functional dyspepsia symptoms in a phase III double-blind, randomized trial.

“This is the first study that demonstrates that rifaximin is efficacious in the treatment of functional dyspepsia, particularly for global dyspeptic symptoms, bloating, and possibly belching. Our finding may suggest a role for the gut microbiota in the pathogenesis of functional dyspepsia,” Dr. Victoria Tan said at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

Rifaximin (Xifaxan) works by reducing or altering bacteria in the gut and has been shown to be efficacious in the treatment of diarrhea-predominant irritable bowel syndrome. It is approved to treat traveler’s diarrhea caused by Escherichia coli and to prevent hepatic encephalopathy.

The study randomly assigned 95 consecutive adults with functional dyspepsia as per ROME III criteria who had a normal gastroscopy within the last 2 years, had active symptoms in the month prior to enrollment, and were Helicobacter pylori negative, to rifaximin 400 mg or placebo three times a day for 2 weeks. In all, 33 rifaximin and 39 placebo patients were evaluable for the primary efficacy outcome of adequate relief of global dyspeptic symptoms (either no or mild dyspeptic symptoms) at any of the follow-up time points.

At baseline, 77% of patients had moderate to severe global dyspepsia symptoms, 74% of the placebo group and 55%% of the rifaximin group had moderate to severe belching, and roughly half of all patients were not on any GI medications. Mean age of the patients was 52 years.

Global dyspepsia symptoms improved with rifaximin beginning at week 2 and significantly favored rifaximin by week 8, with 23.5% of rifaximin patients reporting moderate to severe symptoms compared with 47.4% given placebo (P value = .04), said Dr. Tan of the University of Hong Kong.

Rates of moderate to severe belching were significantly improved with rifaximin at week 4 compared with placebo (14.3% vs. 35.7%; P = .03), but this difference was no longer significant at week 8 (26.5% vs. 29%).

The story was similar for moderate to severe bloating: Rates declined significantly with rifaximin at week 4 (20% vs. 43%; P = .03), but were no longer significant at week 8 (26.5% vs. 34.2%), she said.

A subgroup analysis of female patients showed significant improvements in moderate to severe global dyspeptic symptoms with rifaximin compared with placebo at week 4 (20.8% vs. 59.4%; P = .006) and week 8 (20% vs. 48.4%; P = .048).

Treatment response was not reflected in change in hydrogen breath response, Dr. Tan said. Results of a 3-hour hydrogen breath test performed after a 12-hour overnight fast showed no differences between the rifaximin and placebo groups for H₂ peak above baseline (2.94 ppm vs. 0.11 ppm; P = .29), H₂ area under the curve (+43.64 ppm vs. –49.71 ppm; P = .76), and oro-cecal transit time (24.23 minutes vs. 16.5 minutes; P = .68).

Adverse events were very similar between the two groups at both 4 and 8 weeks, Dr. Tan said. Only one major event occurred, a severe case of acute hepatitis in a woman in the placebo arm who also took traditional Chinese herbs.

[email protected]

On Twitter @pwendl

WASHINGTON – Two weeks of antibiotic therapy with rifaximin provided relief from functional dyspepsia symptoms in a phase III double-blind, randomized trial.

“This is the first study that demonstrates that rifaximin is efficacious in the treatment of functional dyspepsia, particularly for global dyspeptic symptoms, bloating, and possibly belching. Our finding may suggest a role for the gut microbiota in the pathogenesis of functional dyspepsia,” Dr. Victoria Tan said at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

Rifaximin (Xifaxan) works by reducing or altering bacteria in the gut and has been shown to be efficacious in the treatment of diarrhea-predominant irritable bowel syndrome. It is approved to treat traveler’s diarrhea caused by Escherichia coli and to prevent hepatic encephalopathy.

The study randomly assigned 95 consecutive adults with functional dyspepsia as per ROME III criteria who had a normal gastroscopy within the last 2 years, had active symptoms in the month prior to enrollment, and were Helicobacter pylori negative, to rifaximin 400 mg or placebo three times a day for 2 weeks. In all, 33 rifaximin and 39 placebo patients were evaluable for the primary efficacy outcome of adequate relief of global dyspeptic symptoms (either no or mild dyspeptic symptoms) at any of the follow-up time points.

At baseline, 77% of patients had moderate to severe global dyspepsia symptoms, 74% of the placebo group and 55%% of the rifaximin group had moderate to severe belching, and roughly half of all patients were not on any GI medications. Mean age of the patients was 52 years.

Global dyspepsia symptoms improved with rifaximin beginning at week 2 and significantly favored rifaximin by week 8, with 23.5% of rifaximin patients reporting moderate to severe symptoms compared with 47.4% given placebo (P value = .04), said Dr. Tan of the University of Hong Kong.

Rates of moderate to severe belching were significantly improved with rifaximin at week 4 compared with placebo (14.3% vs. 35.7%; P = .03), but this difference was no longer significant at week 8 (26.5% vs. 29%).

The story was similar for moderate to severe bloating: Rates declined significantly with rifaximin at week 4 (20% vs. 43%; P = .03), but were no longer significant at week 8 (26.5% vs. 34.2%), she said.

A subgroup analysis of female patients showed significant improvements in moderate to severe global dyspeptic symptoms with rifaximin compared with placebo at week 4 (20.8% vs. 59.4%; P = .006) and week 8 (20% vs. 48.4%; P = .048).

Treatment response was not reflected in change in hydrogen breath response, Dr. Tan said. Results of a 3-hour hydrogen breath test performed after a 12-hour overnight fast showed no differences between the rifaximin and placebo groups for H₂ peak above baseline (2.94 ppm vs. 0.11 ppm; P = .29), H₂ area under the curve (+43.64 ppm vs. –49.71 ppm; P = .76), and oro-cecal transit time (24.23 minutes vs. 16.5 minutes; P = .68).

Adverse events were very similar between the two groups at both 4 and 8 weeks, Dr. Tan said. Only one major event occurred, a severe case of acute hepatitis in a woman in the placebo arm who also took traditional Chinese herbs.

[email protected]

On Twitter @pwendl

WASHINGTON – Two weeks of antibiotic therapy with rifaximin provided relief from functional dyspepsia symptoms in a phase III double-blind, randomized trial.

“This is the first study that demonstrates that rifaximin is efficacious in the treatment of functional dyspepsia, particularly for global dyspeptic symptoms, bloating, and possibly belching. Our finding may suggest a role for the gut microbiota in the pathogenesis of functional dyspepsia,” Dr. Victoria Tan said at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

Rifaximin (Xifaxan) works by reducing or altering bacteria in the gut and has been shown to be efficacious in the treatment of diarrhea-predominant irritable bowel syndrome. It is approved to treat traveler’s diarrhea caused by Escherichia coli and to prevent hepatic encephalopathy.

The study randomly assigned 95 consecutive adults with functional dyspepsia as per ROME III criteria who had a normal gastroscopy within the last 2 years, had active symptoms in the month prior to enrollment, and were Helicobacter pylori negative, to rifaximin 400 mg or placebo three times a day for 2 weeks. In all, 33 rifaximin and 39 placebo patients were evaluable for the primary efficacy outcome of adequate relief of global dyspeptic symptoms (either no or mild dyspeptic symptoms) at any of the follow-up time points.

At baseline, 77% of patients had moderate to severe global dyspepsia symptoms, 74% of the placebo group and 55%% of the rifaximin group had moderate to severe belching, and roughly half of all patients were not on any GI medications. Mean age of the patients was 52 years.

Global dyspepsia symptoms improved with rifaximin beginning at week 2 and significantly favored rifaximin by week 8, with 23.5% of rifaximin patients reporting moderate to severe symptoms compared with 47.4% given placebo (P value = .04), said Dr. Tan of the University of Hong Kong.

Rates of moderate to severe belching were significantly improved with rifaximin at week 4 compared with placebo (14.3% vs. 35.7%; P = .03), but this difference was no longer significant at week 8 (26.5% vs. 29%).

The story was similar for moderate to severe bloating: Rates declined significantly with rifaximin at week 4 (20% vs. 43%; P = .03), but were no longer significant at week 8 (26.5% vs. 34.2%), she said.

A subgroup analysis of female patients showed significant improvements in moderate to severe global dyspeptic symptoms with rifaximin compared with placebo at week 4 (20.8% vs. 59.4%; P = .006) and week 8 (20% vs. 48.4%; P = .048).

Treatment response was not reflected in change in hydrogen breath response, Dr. Tan said. Results of a 3-hour hydrogen breath test performed after a 12-hour overnight fast showed no differences between the rifaximin and placebo groups for H₂ peak above baseline (2.94 ppm vs. 0.11 ppm; P = .29), H₂ area under the curve (+43.64 ppm vs. –49.71 ppm; P = .76), and oro-cecal transit time (24.23 minutes vs. 16.5 minutes; P = .68).

Adverse events were very similar between the two groups at both 4 and 8 weeks, Dr. Tan said. Only one major event occurred, a severe case of acute hepatitis in a woman in the placebo arm who also took traditional Chinese herbs.

[email protected]

On Twitter @pwendl

WASHINGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

PIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence. In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%. In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time.

Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States. The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHINGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

PIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence. In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%. In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time.

Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States. The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHINGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

PIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence. In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%. In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time.

Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States. The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza (Spain).

Patrice Wendling/Frontline Medical News

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza (Spain).

Patrice Wendling/Frontline Medical News

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza (Spain).

Patrice Wendling/Frontline Medical News

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl