Upper GI Tract

ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.

Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.

Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.

"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.

In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.

Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.

In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.

However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.

There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.

In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.

Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.

The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.

ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.

Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.

Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.

"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.

In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.

Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.

In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.

However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.

There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.

In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.

Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.

The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.

ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.

Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.

Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.

"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.

In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.

Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.

In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.

However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.

There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.

In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.

Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.

The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.

ORLANDO – The tricyclic antidepressant nortriptyline is often prescribed for treatment of nausea, vomiting, and abdominal pain from gastroparesis, but results from a randomized clinical trial suggest that it doesn’t really work, investigators said at the annual Digestive Disease Week.

In a double-masked trial, 15 weeks of treatment with nortriptyline was no better than placebo for management of overall symptoms of idiopathic gastroparesis, reported Dr. Henry P. Parkman from Temple University in Philadelphia.

Although patients started on a 10-mg dose of nortriptyline had early improvement in nausea, this benefit disappeared as the dosage increased. In addition, 19 of the 65 patients assigned to the tricyclic antidepressant (TCA) opted to discontinue treatment early, primarily because of side effects, Dr. Parkman reported.

"Further studies will be needed to determine the role for TCAs and other neuromodulators in patients with idiopathic and also other etiologies of gastroparesis, and also to look at specific symptoms’ improvement associated with TCAs in gastroparesis," he said.

The investigators observed that the practice of treating idiopathic gastroparesis with TCAs is not well supported by clinical evidence, and took it on themselves to see whether they could gather sufficient evidence for or against the efficacy of these agents for this indication.

They chose nortriptyline because of its relatively low anticholinergic side effects, and used a dose-escalating scheme similar to that used in clinical practice.

They enrolled 130 patients into a placebo-controlled, parallel-group trial. Patients randomized to nortriptyline received it at a starting dose of 10 mg daily, which was escalated every 3 weeks to 25, 50, and finally 75 mg.

At the end of the 15 weeks, there were no significant differences between the groups in the primary endpoint, overall symptomatic improvement as measured by change in the 45-point, 9-symptom Gastroparesis Cardinal Symptom Index (GCSI). In all, 15 patients who received the TCA had at least a 50% decline from baseline GCSI score over two consecutive 3-week visits, compared with 14 patients on placebo.

Patients on nortriptyline did have a significant decline in both nausea (P = .04) and abdominal pain (P = .004) at the first visit, but this difference disappeared on subsequent visits.

At the end of the study, patients on the TCA also reported a greater improvement in appetite (P = .03), and showed a nonsignificant trend toward ability to finish a meal (P = .08). Patients on nortriptyline also had a slight gain in body mass index of 0.5 kg/m², compared with a slight loss of –0.2 kg/m² among patients on placebo (P = .03).

More than three times as many patients on nortriptyline stopped treatment early (19 vs. 6, P = .007), primarily because of side effects.

The investigators concluded that the role of TCAs and other neuromodulators for the treatment of idiopathic gastroparesis and other forms of gastrointestinal paralysis needs further exploration.

The study was funded by the National Institutes of Health. Dr. Parkman reported serving on advisory committees and review panels for Tranzyme, and consulting for Evoke, SmartPill, and other companies.

ORLANDO – The tricyclic antidepressant nortriptyline is often prescribed for treatment of nausea, vomiting, and abdominal pain from gastroparesis, but results from a randomized clinical trial suggest that it doesn’t really work, investigators said at the annual Digestive Disease Week.

In a double-masked trial, 15 weeks of treatment with nortriptyline was no better than placebo for management of overall symptoms of idiopathic gastroparesis, reported Dr. Henry P. Parkman from Temple University in Philadelphia.

Although patients started on a 10-mg dose of nortriptyline had early improvement in nausea, this benefit disappeared as the dosage increased. In addition, 19 of the 65 patients assigned to the tricyclic antidepressant (TCA) opted to discontinue treatment early, primarily because of side effects, Dr. Parkman reported.

"Further studies will be needed to determine the role for TCAs and other neuromodulators in patients with idiopathic and also other etiologies of gastroparesis, and also to look at specific symptoms’ improvement associated with TCAs in gastroparesis," he said.

The investigators observed that the practice of treating idiopathic gastroparesis with TCAs is not well supported by clinical evidence, and took it on themselves to see whether they could gather sufficient evidence for or against the efficacy of these agents for this indication.

They chose nortriptyline because of its relatively low anticholinergic side effects, and used a dose-escalating scheme similar to that used in clinical practice.

They enrolled 130 patients into a placebo-controlled, parallel-group trial. Patients randomized to nortriptyline received it at a starting dose of 10 mg daily, which was escalated every 3 weeks to 25, 50, and finally 75 mg.

At the end of the 15 weeks, there were no significant differences between the groups in the primary endpoint, overall symptomatic improvement as measured by change in the 45-point, 9-symptom Gastroparesis Cardinal Symptom Index (GCSI). In all, 15 patients who received the TCA had at least a 50% decline from baseline GCSI score over two consecutive 3-week visits, compared with 14 patients on placebo.

Patients on nortriptyline did have a significant decline in both nausea (P = .04) and abdominal pain (P = .004) at the first visit, but this difference disappeared on subsequent visits.

At the end of the study, patients on the TCA also reported a greater improvement in appetite (P = .03), and showed a nonsignificant trend toward ability to finish a meal (P = .08). Patients on nortriptyline also had a slight gain in body mass index of 0.5 kg/m², compared with a slight loss of –0.2 kg/m² among patients on placebo (P = .03).

More than three times as many patients on nortriptyline stopped treatment early (19 vs. 6, P = .007), primarily because of side effects.

The investigators concluded that the role of TCAs and other neuromodulators for the treatment of idiopathic gastroparesis and other forms of gastrointestinal paralysis needs further exploration.

The study was funded by the National Institutes of Health. Dr. Parkman reported serving on advisory committees and review panels for Tranzyme, and consulting for Evoke, SmartPill, and other companies.

ORLANDO – The tricyclic antidepressant nortriptyline is often prescribed for treatment of nausea, vomiting, and abdominal pain from gastroparesis, but results from a randomized clinical trial suggest that it doesn’t really work, investigators said at the annual Digestive Disease Week.

In a double-masked trial, 15 weeks of treatment with nortriptyline was no better than placebo for management of overall symptoms of idiopathic gastroparesis, reported Dr. Henry P. Parkman from Temple University in Philadelphia.

Although patients started on a 10-mg dose of nortriptyline had early improvement in nausea, this benefit disappeared as the dosage increased. In addition, 19 of the 65 patients assigned to the tricyclic antidepressant (TCA) opted to discontinue treatment early, primarily because of side effects, Dr. Parkman reported.

"Further studies will be needed to determine the role for TCAs and other neuromodulators in patients with idiopathic and also other etiologies of gastroparesis, and also to look at specific symptoms’ improvement associated with TCAs in gastroparesis," he said.

The investigators observed that the practice of treating idiopathic gastroparesis with TCAs is not well supported by clinical evidence, and took it on themselves to see whether they could gather sufficient evidence for or against the efficacy of these agents for this indication.

They chose nortriptyline because of its relatively low anticholinergic side effects, and used a dose-escalating scheme similar to that used in clinical practice.

They enrolled 130 patients into a placebo-controlled, parallel-group trial. Patients randomized to nortriptyline received it at a starting dose of 10 mg daily, which was escalated every 3 weeks to 25, 50, and finally 75 mg.

At the end of the 15 weeks, there were no significant differences between the groups in the primary endpoint, overall symptomatic improvement as measured by change in the 45-point, 9-symptom Gastroparesis Cardinal Symptom Index (GCSI). In all, 15 patients who received the TCA had at least a 50% decline from baseline GCSI score over two consecutive 3-week visits, compared with 14 patients on placebo.

Patients on nortriptyline did have a significant decline in both nausea (P = .04) and abdominal pain (P = .004) at the first visit, but this difference disappeared on subsequent visits.

At the end of the study, patients on the TCA also reported a greater improvement in appetite (P = .03), and showed a nonsignificant trend toward ability to finish a meal (P = .08). Patients on nortriptyline also had a slight gain in body mass index of 0.5 kg/m², compared with a slight loss of –0.2 kg/m² among patients on placebo (P = .03).

More than three times as many patients on nortriptyline stopped treatment early (19 vs. 6, P = .007), primarily because of side effects.

The investigators concluded that the role of TCAs and other neuromodulators for the treatment of idiopathic gastroparesis and other forms of gastrointestinal paralysis needs further exploration.

The study was funded by the National Institutes of Health. Dr. Parkman reported serving on advisory committees and review panels for Tranzyme, and consulting for Evoke, SmartPill, and other companies.

Should you ignore, survey, or ablate Barrett's esophagus? Dr. Prateek Sharma, professor of medicine at the University of Kansas, Kansas City, explains how gastroenterologists can make an accurate diagnosis and provide proper treatment for slightly irregular Z-line, nondysplastic Barrett's esophagus, low-grade dysplasia, and high-grade dysplasia.

For more information on Barrett's esophagus attend the 2013 Freston Conference August 17 and 18 in Chicago.

Should you ignore, survey, or ablate Barrett's esophagus? Dr. Prateek Sharma, professor of medicine at the University of Kansas, Kansas City, explains how gastroenterologists can make an accurate diagnosis and provide proper treatment for slightly irregular Z-line, nondysplastic Barrett's esophagus, low-grade dysplasia, and high-grade dysplasia.

For more information on Barrett's esophagus attend the 2013 Freston Conference August 17 and 18 in Chicago.

Should you ignore, survey, or ablate Barrett's esophagus? Dr. Prateek Sharma, professor of medicine at the University of Kansas, Kansas City, explains how gastroenterologists can make an accurate diagnosis and provide proper treatment for slightly irregular Z-line, nondysplastic Barrett's esophagus, low-grade dysplasia, and high-grade dysplasia.

For more information on Barrett's esophagus attend the 2013 Freston Conference August 17 and 18 in Chicago.

Among chronic nonsteroidal anti-inflammatory patients at high risk for a gastrointestinal bleeding, only two-thirds continue to be prescribed a proton pump inhibitor after 2 years.

Moreover, patients whose PPI prescriptions were discontinued were significantly more likely to experience a GI adverse event, compared with patients who had continuous NSAID and PPI coprescription, wrote Dr. Isabelle Le Ray and colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.12.016).

Dr. Le Ray, of the Centre Hospitalier Universitaire de Dijon, France, and colleagues looked at records from the Longitudinal Patient Database, which collects data from a representative sample of 1,200 general practitioners in France.

Specifically, Dr. Le Ray focused on high-risk patients within the database who received a prescription for an NSAID for more than 7 days in 2007 plus a PPI, who renewed their NSAID within 6 months following the last prescription over a 2-year period.

Patients were considered to be high risk for a GI bleed if they were aged 65 years or older, had a history of upper GI disease, a co-prescription with an anticoagulant or antiplatelet medication, a previous bleed, and other comorbid conditions like rheumatoid arthritis.

A total of 1,856 patients met the criteria; most (74.4%) were over age 65, and 63.8% were female.

Although more than 14 different NSAIDs were prescribed, diclofenac, ketoprofen, piroxicam, and celecoxib accounted for the bulk of prescriptions. The median number of NSAID renewals during the 2-year period was 8, with a median of 30 days duration for each prescription.

According to the authors, at 12 months after initial NSAID/PPI prescription, the persistence probability of still having an active PPI prescription fell to 0.77(95% confidence interval, 0.75-0.79).

By 2 years, that likelihood fell to 0.68 (95% CI, 0.66-0.70).

The authors then looked at the presence of GI adverse events in this cohort. They found that 379 patients experienced an event, with patients who were not persistently prescribed a PPI at significantly higher risk, compared with patients whose PPI prescriptions never lapsed (odds ratio = 1.45; 95% CI, 1.06-2.09, P = .02).

"Absolute risk reduction associated with a continuous prescription of PPI with NSAIDs, in at-risk patients, was 3.2%," wrote the authors.

According to the researchers, factors associated with discontinuing a PPI included change from a given NSAID to a COX-2 inhibitor (multivariate hazard ratio for PPI discontinuation, 2.50; 95% CI, 1.91-3.28), despite the fact that "international guidelines recommend coprescription of a PPI for at-risk patients, even when using a COX-2 selective agent."

Being female also carried a high risk of stopping PPI treatment, (HR 1.25; 95%CI 1.05-1.49), while having multiple prescriptions for other drugs decreased the risk of PPI discontinuation (HR for stopping PPI 0.94 for each additional treatment; 95% CI, 0.91-0.96).

The study represents "the first time that the persistence of a prescription, i.e. systematic renewal of the [gastroprotective agent, the PPI] when the NSAID is being renewed, over time is characterized," the researchers said.

"These data suggest that the optimizing of [gastroprotective agent] coverage, mostly with a PPI, remains a major health issue among chronic NSAID users," they added.

The authors disclosed that this study was funded by the pharmaceutical company Ethypharm, for which one investigator is also an employee and another has served as a paid consultant. They added that this paper discusses no medications manufactured by Ethypharm.

Among chronic nonsteroidal anti-inflammatory patients at high risk for a gastrointestinal bleeding, only two-thirds continue to be prescribed a proton pump inhibitor after 2 years.

Moreover, patients whose PPI prescriptions were discontinued were significantly more likely to experience a GI adverse event, compared with patients who had continuous NSAID and PPI coprescription, wrote Dr. Isabelle Le Ray and colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.12.016).

Dr. Le Ray, of the Centre Hospitalier Universitaire de Dijon, France, and colleagues looked at records from the Longitudinal Patient Database, which collects data from a representative sample of 1,200 general practitioners in France.

Specifically, Dr. Le Ray focused on high-risk patients within the database who received a prescription for an NSAID for more than 7 days in 2007 plus a PPI, who renewed their NSAID within 6 months following the last prescription over a 2-year period.

Patients were considered to be high risk for a GI bleed if they were aged 65 years or older, had a history of upper GI disease, a co-prescription with an anticoagulant or antiplatelet medication, a previous bleed, and other comorbid conditions like rheumatoid arthritis.

A total of 1,856 patients met the criteria; most (74.4%) were over age 65, and 63.8% were female.

Although more than 14 different NSAIDs were prescribed, diclofenac, ketoprofen, piroxicam, and celecoxib accounted for the bulk of prescriptions. The median number of NSAID renewals during the 2-year period was 8, with a median of 30 days duration for each prescription.

According to the authors, at 12 months after initial NSAID/PPI prescription, the persistence probability of still having an active PPI prescription fell to 0.77(95% confidence interval, 0.75-0.79).

By 2 years, that likelihood fell to 0.68 (95% CI, 0.66-0.70).

The authors then looked at the presence of GI adverse events in this cohort. They found that 379 patients experienced an event, with patients who were not persistently prescribed a PPI at significantly higher risk, compared with patients whose PPI prescriptions never lapsed (odds ratio = 1.45; 95% CI, 1.06-2.09, P = .02).

"Absolute risk reduction associated with a continuous prescription of PPI with NSAIDs, in at-risk patients, was 3.2%," wrote the authors.

According to the researchers, factors associated with discontinuing a PPI included change from a given NSAID to a COX-2 inhibitor (multivariate hazard ratio for PPI discontinuation, 2.50; 95% CI, 1.91-3.28), despite the fact that "international guidelines recommend coprescription of a PPI for at-risk patients, even when using a COX-2 selective agent."

Being female also carried a high risk of stopping PPI treatment, (HR 1.25; 95%CI 1.05-1.49), while having multiple prescriptions for other drugs decreased the risk of PPI discontinuation (HR for stopping PPI 0.94 for each additional treatment; 95% CI, 0.91-0.96).

The study represents "the first time that the persistence of a prescription, i.e. systematic renewal of the [gastroprotective agent, the PPI] when the NSAID is being renewed, over time is characterized," the researchers said.

"These data suggest that the optimizing of [gastroprotective agent] coverage, mostly with a PPI, remains a major health issue among chronic NSAID users," they added.

The authors disclosed that this study was funded by the pharmaceutical company Ethypharm, for which one investigator is also an employee and another has served as a paid consultant. They added that this paper discusses no medications manufactured by Ethypharm.

Among chronic nonsteroidal anti-inflammatory patients at high risk for a gastrointestinal bleeding, only two-thirds continue to be prescribed a proton pump inhibitor after 2 years.

Moreover, patients whose PPI prescriptions were discontinued were significantly more likely to experience a GI adverse event, compared with patients who had continuous NSAID and PPI coprescription, wrote Dr. Isabelle Le Ray and colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.12.016).

Dr. Le Ray, of the Centre Hospitalier Universitaire de Dijon, France, and colleagues looked at records from the Longitudinal Patient Database, which collects data from a representative sample of 1,200 general practitioners in France.

Specifically, Dr. Le Ray focused on high-risk patients within the database who received a prescription for an NSAID for more than 7 days in 2007 plus a PPI, who renewed their NSAID within 6 months following the last prescription over a 2-year period.

Patients were considered to be high risk for a GI bleed if they were aged 65 years or older, had a history of upper GI disease, a co-prescription with an anticoagulant or antiplatelet medication, a previous bleed, and other comorbid conditions like rheumatoid arthritis.

A total of 1,856 patients met the criteria; most (74.4%) were over age 65, and 63.8% were female.

Although more than 14 different NSAIDs were prescribed, diclofenac, ketoprofen, piroxicam, and celecoxib accounted for the bulk of prescriptions. The median number of NSAID renewals during the 2-year period was 8, with a median of 30 days duration for each prescription.

According to the authors, at 12 months after initial NSAID/PPI prescription, the persistence probability of still having an active PPI prescription fell to 0.77(95% confidence interval, 0.75-0.79).

By 2 years, that likelihood fell to 0.68 (95% CI, 0.66-0.70).

The authors then looked at the presence of GI adverse events in this cohort. They found that 379 patients experienced an event, with patients who were not persistently prescribed a PPI at significantly higher risk, compared with patients whose PPI prescriptions never lapsed (odds ratio = 1.45; 95% CI, 1.06-2.09, P = .02).

"Absolute risk reduction associated with a continuous prescription of PPI with NSAIDs, in at-risk patients, was 3.2%," wrote the authors.

According to the researchers, factors associated with discontinuing a PPI included change from a given NSAID to a COX-2 inhibitor (multivariate hazard ratio for PPI discontinuation, 2.50; 95% CI, 1.91-3.28), despite the fact that "international guidelines recommend coprescription of a PPI for at-risk patients, even when using a COX-2 selective agent."

Being female also carried a high risk of stopping PPI treatment, (HR 1.25; 95%CI 1.05-1.49), while having multiple prescriptions for other drugs decreased the risk of PPI discontinuation (HR for stopping PPI 0.94 for each additional treatment; 95% CI, 0.91-0.96).

The study represents "the first time that the persistence of a prescription, i.e. systematic renewal of the [gastroprotective agent, the PPI] when the NSAID is being renewed, over time is characterized," the researchers said.

"These data suggest that the optimizing of [gastroprotective agent] coverage, mostly with a PPI, remains a major health issue among chronic NSAID users," they added.

The authors disclosed that this study was funded by the pharmaceutical company Ethypharm, for which one investigator is also an employee and another has served as a paid consultant. They added that this paper discusses no medications manufactured by Ethypharm.

HONOLULU  – A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastroduodenal ulcers and treatment discontinuations than conventional enteric-coated aspirin in patients on antiplatelet therapy for secondary prevention of cerebrovascular events.

Two double-blind, 6-month, randomized phase III clinical trials totaling 1,049 patients with an indication for daily aspirin for secondary cardiovascular or cerebrovascular prevention included 215 subjects with prior ischemic stroke or transient ischemic attack (TIA). All participants in the phase III trials were at risk for upper GI ulcers by virtue of being at least 55 years of age or having a documented history of gastric or duodenal ulcer within 5 years prior to enrollment. Baseline endoscopy was negative in all subjects.

Study participants were randomized to conventional enteric-coated aspirin at 325 mg/day or to the investigational tablet, known for now as PA32540. This once-daily tablet contains 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin, Dr. Mark J. Alberts explained at the International Stroke Conference sponsored by the American Heart Association.

He focused on the 215 study participants on aspirin for secondary cerebrovascular prevention. The primary study endpoint – the incidence of endoscopically confirmed gastroduodenal ulcers – occurred in 2.0% of patients on PA32540, compared with 12.4% of controls on enteric-coated aspirin.

Moreover, discontinuation of therapy due to dyspepsia, erosive gastritis, or other prespecified upper GI events occurred in 8% of controls and in none of the participants on the combo tablet, reported Dr. Alberts, professor of neurology at Northwestern University, Chicago, and director of the stroke program at Northwestern Memorial Hospital.

The major adverse cardiovascular event rate over the course of 6 months was 2.9% in the PA32540 group and 4.4% with enteric-coated aspirin, a nonsignificant difference.

These study findings support the hypothesis that a single tablet formulation of aspirin and GI-protective omeprazole may safely improve long-term compliance with aspirin therapy in patients at increased risk for upper GI toxicity, Dr. Alberts observed.

Pozen, which sponsored the phase III trials, has announced it will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary cardiovascular and cerebrovascular prevention in the roughly 15% of patients at risk for aspirin-induced upper GI adverse events. The company is currently seeking strategic partners to help market the novel product on a wide scale at an affordable price after PA32540 receives regulatory approval.

Dr. Alberts reported serving as a consultant to Pozen.

bjancin@frontlinemedcom.com

HONOLULU  – A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastroduodenal ulcers and treatment discontinuations than conventional enteric-coated aspirin in patients on antiplatelet therapy for secondary prevention of cerebrovascular events.

Two double-blind, 6-month, randomized phase III clinical trials totaling 1,049 patients with an indication for daily aspirin for secondary cardiovascular or cerebrovascular prevention included 215 subjects with prior ischemic stroke or transient ischemic attack (TIA). All participants in the phase III trials were at risk for upper GI ulcers by virtue of being at least 55 years of age or having a documented history of gastric or duodenal ulcer within 5 years prior to enrollment. Baseline endoscopy was negative in all subjects.

Study participants were randomized to conventional enteric-coated aspirin at 325 mg/day or to the investigational tablet, known for now as PA32540. This once-daily tablet contains 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin, Dr. Mark J. Alberts explained at the International Stroke Conference sponsored by the American Heart Association.

He focused on the 215 study participants on aspirin for secondary cerebrovascular prevention. The primary study endpoint – the incidence of endoscopically confirmed gastroduodenal ulcers – occurred in 2.0% of patients on PA32540, compared with 12.4% of controls on enteric-coated aspirin.

Moreover, discontinuation of therapy due to dyspepsia, erosive gastritis, or other prespecified upper GI events occurred in 8% of controls and in none of the participants on the combo tablet, reported Dr. Alberts, professor of neurology at Northwestern University, Chicago, and director of the stroke program at Northwestern Memorial Hospital.

The major adverse cardiovascular event rate over the course of 6 months was 2.9% in the PA32540 group and 4.4% with enteric-coated aspirin, a nonsignificant difference.

These study findings support the hypothesis that a single tablet formulation of aspirin and GI-protective omeprazole may safely improve long-term compliance with aspirin therapy in patients at increased risk for upper GI toxicity, Dr. Alberts observed.

Pozen, which sponsored the phase III trials, has announced it will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary cardiovascular and cerebrovascular prevention in the roughly 15% of patients at risk for aspirin-induced upper GI adverse events. The company is currently seeking strategic partners to help market the novel product on a wide scale at an affordable price after PA32540 receives regulatory approval.

Dr. Alberts reported serving as a consultant to Pozen.

bjancin@frontlinemedcom.com

HONOLULU  – A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastroduodenal ulcers and treatment discontinuations than conventional enteric-coated aspirin in patients on antiplatelet therapy for secondary prevention of cerebrovascular events.

Two double-blind, 6-month, randomized phase III clinical trials totaling 1,049 patients with an indication for daily aspirin for secondary cardiovascular or cerebrovascular prevention included 215 subjects with prior ischemic stroke or transient ischemic attack (TIA). All participants in the phase III trials were at risk for upper GI ulcers by virtue of being at least 55 years of age or having a documented history of gastric or duodenal ulcer within 5 years prior to enrollment. Baseline endoscopy was negative in all subjects.

Study participants were randomized to conventional enteric-coated aspirin at 325 mg/day or to the investigational tablet, known for now as PA32540. This once-daily tablet contains 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin, Dr. Mark J. Alberts explained at the International Stroke Conference sponsored by the American Heart Association.

He focused on the 215 study participants on aspirin for secondary cerebrovascular prevention. The primary study endpoint – the incidence of endoscopically confirmed gastroduodenal ulcers – occurred in 2.0% of patients on PA32540, compared with 12.4% of controls on enteric-coated aspirin.

Moreover, discontinuation of therapy due to dyspepsia, erosive gastritis, or other prespecified upper GI events occurred in 8% of controls and in none of the participants on the combo tablet, reported Dr. Alberts, professor of neurology at Northwestern University, Chicago, and director of the stroke program at Northwestern Memorial Hospital.

The major adverse cardiovascular event rate over the course of 6 months was 2.9% in the PA32540 group and 4.4% with enteric-coated aspirin, a nonsignificant difference.

These study findings support the hypothesis that a single tablet formulation of aspirin and GI-protective omeprazole may safely improve long-term compliance with aspirin therapy in patients at increased risk for upper GI toxicity, Dr. Alberts observed.

Pozen, which sponsored the phase III trials, has announced it will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary cardiovascular and cerebrovascular prevention in the roughly 15% of patients at risk for aspirin-induced upper GI adverse events. The company is currently seeking strategic partners to help market the novel product on a wide scale at an affordable price after PA32540 receives regulatory approval.

Dr. Alberts reported serving as a consultant to Pozen.

bjancin@frontlinemedcom.com

Proton pump inhibitors resolve symptoms of gastroesophageal reflux disease and promote healing of erosive esophagitis regardless of a patient’s body mass index, according to a new study.

However, research findings "suggest that obese or overweight patients may be at a greater risk of advanced grades of erosive esophagitis than patients with normal weight," reported Dr. Prateek Sharma of the University of Kansas, Kansas City, Mo., and his associates (J. Clin. Gastroenterol. 2013 Feb. 24 [doi: 10.1097/MCG.0b013e31827e46be]).

Other factors such as PPI treatment and older age may also influence the odds of symptom resolution in nonerosive reflux disease (NERD) and erosive esophagitis patients.

Investigators conducted two post hoc retrospective analyses of pooled data from randomized, double-blind, multicenter studies of patients with GERD treated with PPIs.

The first analysis consisted of two studies assessing 704 subjects with NERD who received esomeprazole 20 mg (n = 228), esomeprazole 40 mg (n = 238) or placebo (n = 238).

The second analysis pooled data from five studies of 11,027 patients with erosive esophagitis treated with esomeprazole 40 mg (n = 5,519), omeprazole 20 mg (n = 2,407), or lansoprazole 30 mg (n = 3,101).

Patients were analyzed in three groups: normal weight, overweight, and obese, defined as BMI <25 kg/m², 25 to <35 kg/m², and greater than or equal to 35 kg/m², respectively.

Analysis 1 demonstrated that BMI had no effect on baseline heartburn in patients with NERD (P = .28). Specifically, 21.4% of overweight and obese individuals had no heartburn symptoms at baseline, while 35.9%, 32.5%, and 10.2% had mild, moderate, and severe symptoms, respectively. In comparison, 14.3% of patients at a normal weight had no heartburn, while 38.4%, 37.9%, and 9.4%, had mild, moderate, and severe symptoms, respectively.

In Analysis 2, however, 34.7% of patients who were overweight and 32% who were obese had Los Angeles (LA) grade C or D erosive esophagitis compared with 25.5% of normal weight subjects (P < .0001). At baseline, 34.2% of overweight or obese patients had LA grade C or D of the condition.

Heartburn resolution was similar in all NERD BMI subgroups. Symptoms were successfully treated in 36.5%, 36.7%, and 32.3% of normal weight, overweight, and obese individuals taking PPIs, respectively. Healing rates with PPIs were also similar across weight categories and within erosive esophagitis LA grade.

Further analysis with logistic regression models indicated that BMI did not influence resolution of heartburn (odds ratio [OR] =1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis healing (OR = 1.01; 95% CI, 1.00-1.02; P = .23).

However, the odds of heartburn resolution increased with esomeprazole 20 mg vs. placebo (OR = 4.26, 2.63-6.88, P < .0001), esomeprazole 40 mg vs. placebo (OR = 4.0, 2.48-6.44, P < .0001), older age (OR=1.0, 1.0-1.0, P = .0041), and in men vs. women (OR = 1.50, 1.04-2.14, P = .0284).

Additionally, the chance of erosive esophagitis healing increased with esomeprazole 40 mg vs. omeprazole 20 mg (OR = 1.70, 1.44-2.01, P < .0001), lansoprazole 30 mg vs. omeprazole 20 mg (OR = 1.30, 1.05-1.62, P = .0183), older age (OR = 1.02, 1.01-1.02, P < .0001), in black vs. white patients (OR = 0.67, 0.54-0.84, P = .0003), and hiatal hernia (OR = 1.21, 1.08-1.35, P = .0011).

The odds of erosive esophagitis healing were greater in patients with LA grade A vs. D (OR = 4.54, 3.71-5.55, P < .0001) than in patients with LA grade B vs. D (OR = 2.76, 2.30-3.32, P < .0001) or C vs. D (OR = 1.70, 1.42-2.03, P < .0001).

While this pooled analysis is limited because "data were obtained from post hoc analyses of clinical efficacy studies not designed to evaluate the effects of obesity on GERD symptom severity or treatment success," the research has "considerable statistical power" due to the large number of patients included, the investigators wrote.

The study was supported by AstraZeneca LP, in Wilmington, Del. Dr. Sharma receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda. His coauthors disclosed ties to various pharmaceutical companies, including AstraZeneca.

Proton pump inhibitors resolve symptoms of gastroesophageal reflux disease and promote healing of erosive esophagitis regardless of a patient’s body mass index, according to a new study.

However, research findings "suggest that obese or overweight patients may be at a greater risk of advanced grades of erosive esophagitis than patients with normal weight," reported Dr. Prateek Sharma of the University of Kansas, Kansas City, Mo., and his associates (J. Clin. Gastroenterol. 2013 Feb. 24 [doi: 10.1097/MCG.0b013e31827e46be]).

Other factors such as PPI treatment and older age may also influence the odds of symptom resolution in nonerosive reflux disease (NERD) and erosive esophagitis patients.

Investigators conducted two post hoc retrospective analyses of pooled data from randomized, double-blind, multicenter studies of patients with GERD treated with PPIs.

The first analysis consisted of two studies assessing 704 subjects with NERD who received esomeprazole 20 mg (n = 228), esomeprazole 40 mg (n = 238) or placebo (n = 238).

The second analysis pooled data from five studies of 11,027 patients with erosive esophagitis treated with esomeprazole 40 mg (n = 5,519), omeprazole 20 mg (n = 2,407), or lansoprazole 30 mg (n = 3,101).

Patients were analyzed in three groups: normal weight, overweight, and obese, defined as BMI <25 kg/m², 25 to <35 kg/m², and greater than or equal to 35 kg/m², respectively.

Analysis 1 demonstrated that BMI had no effect on baseline heartburn in patients with NERD (P = .28). Specifically, 21.4% of overweight and obese individuals had no heartburn symptoms at baseline, while 35.9%, 32.5%, and 10.2% had mild, moderate, and severe symptoms, respectively. In comparison, 14.3% of patients at a normal weight had no heartburn, while 38.4%, 37.9%, and 9.4%, had mild, moderate, and severe symptoms, respectively.

In Analysis 2, however, 34.7% of patients who were overweight and 32% who were obese had Los Angeles (LA) grade C or D erosive esophagitis compared with 25.5% of normal weight subjects (P < .0001). At baseline, 34.2% of overweight or obese patients had LA grade C or D of the condition.

Heartburn resolution was similar in all NERD BMI subgroups. Symptoms were successfully treated in 36.5%, 36.7%, and 32.3% of normal weight, overweight, and obese individuals taking PPIs, respectively. Healing rates with PPIs were also similar across weight categories and within erosive esophagitis LA grade.

Further analysis with logistic regression models indicated that BMI did not influence resolution of heartburn (odds ratio [OR] =1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis healing (OR = 1.01; 95% CI, 1.00-1.02; P = .23).

However, the odds of heartburn resolution increased with esomeprazole 20 mg vs. placebo (OR = 4.26, 2.63-6.88, P < .0001), esomeprazole 40 mg vs. placebo (OR = 4.0, 2.48-6.44, P < .0001), older age (OR=1.0, 1.0-1.0, P = .0041), and in men vs. women (OR = 1.50, 1.04-2.14, P = .0284).

Additionally, the chance of erosive esophagitis healing increased with esomeprazole 40 mg vs. omeprazole 20 mg (OR = 1.70, 1.44-2.01, P < .0001), lansoprazole 30 mg vs. omeprazole 20 mg (OR = 1.30, 1.05-1.62, P = .0183), older age (OR = 1.02, 1.01-1.02, P < .0001), in black vs. white patients (OR = 0.67, 0.54-0.84, P = .0003), and hiatal hernia (OR = 1.21, 1.08-1.35, P = .0011).

The odds of erosive esophagitis healing were greater in patients with LA grade A vs. D (OR = 4.54, 3.71-5.55, P < .0001) than in patients with LA grade B vs. D (OR = 2.76, 2.30-3.32, P < .0001) or C vs. D (OR = 1.70, 1.42-2.03, P < .0001).

While this pooled analysis is limited because "data were obtained from post hoc analyses of clinical efficacy studies not designed to evaluate the effects of obesity on GERD symptom severity or treatment success," the research has "considerable statistical power" due to the large number of patients included, the investigators wrote.

The study was supported by AstraZeneca LP, in Wilmington, Del. Dr. Sharma receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda. His coauthors disclosed ties to various pharmaceutical companies, including AstraZeneca.

Proton pump inhibitors resolve symptoms of gastroesophageal reflux disease and promote healing of erosive esophagitis regardless of a patient’s body mass index, according to a new study.

However, research findings "suggest that obese or overweight patients may be at a greater risk of advanced grades of erosive esophagitis than patients with normal weight," reported Dr. Prateek Sharma of the University of Kansas, Kansas City, Mo., and his associates (J. Clin. Gastroenterol. 2013 Feb. 24 [doi: 10.1097/MCG.0b013e31827e46be]).

Other factors such as PPI treatment and older age may also influence the odds of symptom resolution in nonerosive reflux disease (NERD) and erosive esophagitis patients.

Investigators conducted two post hoc retrospective analyses of pooled data from randomized, double-blind, multicenter studies of patients with GERD treated with PPIs.

The first analysis consisted of two studies assessing 704 subjects with NERD who received esomeprazole 20 mg (n = 228), esomeprazole 40 mg (n = 238) or placebo (n = 238).

The second analysis pooled data from five studies of 11,027 patients with erosive esophagitis treated with esomeprazole 40 mg (n = 5,519), omeprazole 20 mg (n = 2,407), or lansoprazole 30 mg (n = 3,101).

Patients were analyzed in three groups: normal weight, overweight, and obese, defined as BMI <25 kg/m², 25 to <35 kg/m², and greater than or equal to 35 kg/m², respectively.

Analysis 1 demonstrated that BMI had no effect on baseline heartburn in patients with NERD (P = .28). Specifically, 21.4% of overweight and obese individuals had no heartburn symptoms at baseline, while 35.9%, 32.5%, and 10.2% had mild, moderate, and severe symptoms, respectively. In comparison, 14.3% of patients at a normal weight had no heartburn, while 38.4%, 37.9%, and 9.4%, had mild, moderate, and severe symptoms, respectively.

In Analysis 2, however, 34.7% of patients who were overweight and 32% who were obese had Los Angeles (LA) grade C or D erosive esophagitis compared with 25.5% of normal weight subjects (P < .0001). At baseline, 34.2% of overweight or obese patients had LA grade C or D of the condition.

Heartburn resolution was similar in all NERD BMI subgroups. Symptoms were successfully treated in 36.5%, 36.7%, and 32.3% of normal weight, overweight, and obese individuals taking PPIs, respectively. Healing rates with PPIs were also similar across weight categories and within erosive esophagitis LA grade.

Further analysis with logistic regression models indicated that BMI did not influence resolution of heartburn (odds ratio [OR] =1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis healing (OR = 1.01; 95% CI, 1.00-1.02; P = .23).

However, the odds of heartburn resolution increased with esomeprazole 20 mg vs. placebo (OR = 4.26, 2.63-6.88, P < .0001), esomeprazole 40 mg vs. placebo (OR = 4.0, 2.48-6.44, P < .0001), older age (OR=1.0, 1.0-1.0, P = .0041), and in men vs. women (OR = 1.50, 1.04-2.14, P = .0284).

Additionally, the chance of erosive esophagitis healing increased with esomeprazole 40 mg vs. omeprazole 20 mg (OR = 1.70, 1.44-2.01, P < .0001), lansoprazole 30 mg vs. omeprazole 20 mg (OR = 1.30, 1.05-1.62, P = .0183), older age (OR = 1.02, 1.01-1.02, P < .0001), in black vs. white patients (OR = 0.67, 0.54-0.84, P = .0003), and hiatal hernia (OR = 1.21, 1.08-1.35, P = .0011).

The odds of erosive esophagitis healing were greater in patients with LA grade A vs. D (OR = 4.54, 3.71-5.55, P < .0001) than in patients with LA grade B vs. D (OR = 2.76, 2.30-3.32, P < .0001) or C vs. D (OR = 1.70, 1.42-2.03, P < .0001).

While this pooled analysis is limited because "data were obtained from post hoc analyses of clinical efficacy studies not designed to evaluate the effects of obesity on GERD symptom severity or treatment success," the research has "considerable statistical power" due to the large number of patients included, the investigators wrote.

The study was supported by AstraZeneca LP, in Wilmington, Del. Dr. Sharma receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda. His coauthors disclosed ties to various pharmaceutical companies, including AstraZeneca.

In achalasia, manometric subtype II patients have the greatest treatment success rates, compared with type I and type III patients.

Moreover, the finding applies both to patients treated with pneumatic dilation and to those treated with laparoscopic Heller myotomy, which have comparable high success rates in this population, reported Dr. Wout O. Rohof and Dr. Renato Salvador in the April issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.027).

Lead coauthors Dr. Rohof and Dr. Salvador, from the Academic Medical Center in Amsterdam and the Padova (Italy) University Hospital, respectively, and their colleagues looked at data from nearly 200 patients who participated in the previously published European Achalasia Trial (N. Engl. J. Med. 2011;364:1807-16).

In that study, 201 patients were randomly assigned to undergo either pneumatic dilation or Heller myotomy, with the result being that both treatments produced equally high success rates in achalasia patients.

In the current study, the investigators looked at the 176 patients for whom pretreatment conventional myometric grading was available, to see whether treatment response rates were higher in subtype I, II, or III.

Briefly, according to Pandolfino et al., subtype I refers to patients in whom the esophageal body exhibits minimal contractility; type II to patients who lack peristalsis but demonstrate intermittent periods of compartmentalized esophageal pressurization; and type III to patients who exhibit spastic contractions in the distal esophagus (Gastroenterology 2008;135:1526-33).

Overall, 44 patients (25%) had achalasia type I, 114 (65%) had type II, and 18 (10%) type III.

In the European Achalasia Trial, there were no statistically significant differences in age or sex between patient subtypes, and subtypes were equally distributed over the two treatment protocols, wrote the authors.

The researchers found that among type I patients, there was no significant difference in success rates between dilation and myotomy (81% vs. 85%, respectively; P less than .01), with success defined as a drop in Eckardt score to 3 or less at 1 year post treatment.

"In contrast, in type II, the success rate for dilation was significantly higher than that of myotomy, ... with 100% treatment success in the [dilation] group, compared to 93% in the [myotomy] group," the authors wrote (P less than .05).

Type III patients, in contrast, had overall lower success rates, with 86% for myotomy and 40% for dilation (the difference between the groups could not be assessed for significance because there were too few patients with type III achalasia).

In any case, "irrespective of treatment arm, success rate after a mean follow-up of 43 months was significantly higher in patients with type II compared to type I (P less than .01) and type III (P less than .001)," the researchers wrote.

The authors conceded that the manometry subtype classification system developed by Pandolfino was designed for use with high-resolution manometry instead of the conventional manometry used in their study.

They noted, however, that at least one study has found 100% agreement between the classification of subtypes based on conventional pressure line tracings versus high-resolution manometry plots, and "our three patient groups were similar to those reported by Pandolfino, in terms of both clinical features and outcome after therapy."

Indeed, "based on our findings, we conclude that when a graded distension protocol allowing redilation is used, pneumatic dilation and laparoscopic Heller myotomy are both appropriate treatment options for type I and type II achalasia, at least until longer follow-up data are available," the authors concluded.

The researchers stated that they had no competing interests to disclose in relation to this study. One of the authors disclosed being funded by a grant from the Flemish government.

In achalasia, manometric subtype II patients have the greatest treatment success rates, compared with type I and type III patients.

Moreover, the finding applies both to patients treated with pneumatic dilation and to those treated with laparoscopic Heller myotomy, which have comparable high success rates in this population, reported Dr. Wout O. Rohof and Dr. Renato Salvador in the April issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.027).

Lead coauthors Dr. Rohof and Dr. Salvador, from the Academic Medical Center in Amsterdam and the Padova (Italy) University Hospital, respectively, and their colleagues looked at data from nearly 200 patients who participated in the previously published European Achalasia Trial (N. Engl. J. Med. 2011;364:1807-16).

In that study, 201 patients were randomly assigned to undergo either pneumatic dilation or Heller myotomy, with the result being that both treatments produced equally high success rates in achalasia patients.

In the current study, the investigators looked at the 176 patients for whom pretreatment conventional myometric grading was available, to see whether treatment response rates were higher in subtype I, II, or III.

Briefly, according to Pandolfino et al., subtype I refers to patients in whom the esophageal body exhibits minimal contractility; type II to patients who lack peristalsis but demonstrate intermittent periods of compartmentalized esophageal pressurization; and type III to patients who exhibit spastic contractions in the distal esophagus (Gastroenterology 2008;135:1526-33).

Overall, 44 patients (25%) had achalasia type I, 114 (65%) had type II, and 18 (10%) type III.

In the European Achalasia Trial, there were no statistically significant differences in age or sex between patient subtypes, and subtypes were equally distributed over the two treatment protocols, wrote the authors.

The researchers found that among type I patients, there was no significant difference in success rates between dilation and myotomy (81% vs. 85%, respectively; P less than .01), with success defined as a drop in Eckardt score to 3 or less at 1 year post treatment.

"In contrast, in type II, the success rate for dilation was significantly higher than that of myotomy, ... with 100% treatment success in the [dilation] group, compared to 93% in the [myotomy] group," the authors wrote (P less than .05).

Type III patients, in contrast, had overall lower success rates, with 86% for myotomy and 40% for dilation (the difference between the groups could not be assessed for significance because there were too few patients with type III achalasia).

In any case, "irrespective of treatment arm, success rate after a mean follow-up of 43 months was significantly higher in patients with type II compared to type I (P less than .01) and type III (P less than .001)," the researchers wrote.

The authors conceded that the manometry subtype classification system developed by Pandolfino was designed for use with high-resolution manometry instead of the conventional manometry used in their study.

They noted, however, that at least one study has found 100% agreement between the classification of subtypes based on conventional pressure line tracings versus high-resolution manometry plots, and "our three patient groups were similar to those reported by Pandolfino, in terms of both clinical features and outcome after therapy."

Indeed, "based on our findings, we conclude that when a graded distension protocol allowing redilation is used, pneumatic dilation and laparoscopic Heller myotomy are both appropriate treatment options for type I and type II achalasia, at least until longer follow-up data are available," the authors concluded.

The researchers stated that they had no competing interests to disclose in relation to this study. One of the authors disclosed being funded by a grant from the Flemish government.

In achalasia, manometric subtype II patients have the greatest treatment success rates, compared with type I and type III patients.

Moreover, the finding applies both to patients treated with pneumatic dilation and to those treated with laparoscopic Heller myotomy, which have comparable high success rates in this population, reported Dr. Wout O. Rohof and Dr. Renato Salvador in the April issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.027).

Lead coauthors Dr. Rohof and Dr. Salvador, from the Academic Medical Center in Amsterdam and the Padova (Italy) University Hospital, respectively, and their colleagues looked at data from nearly 200 patients who participated in the previously published European Achalasia Trial (N. Engl. J. Med. 2011;364:1807-16).

In that study, 201 patients were randomly assigned to undergo either pneumatic dilation or Heller myotomy, with the result being that both treatments produced equally high success rates in achalasia patients.

In the current study, the investigators looked at the 176 patients for whom pretreatment conventional myometric grading was available, to see whether treatment response rates were higher in subtype I, II, or III.

Briefly, according to Pandolfino et al., subtype I refers to patients in whom the esophageal body exhibits minimal contractility; type II to patients who lack peristalsis but demonstrate intermittent periods of compartmentalized esophageal pressurization; and type III to patients who exhibit spastic contractions in the distal esophagus (Gastroenterology 2008;135:1526-33).

Overall, 44 patients (25%) had achalasia type I, 114 (65%) had type II, and 18 (10%) type III.

In the European Achalasia Trial, there were no statistically significant differences in age or sex between patient subtypes, and subtypes were equally distributed over the two treatment protocols, wrote the authors.

The researchers found that among type I patients, there was no significant difference in success rates between dilation and myotomy (81% vs. 85%, respectively; P less than .01), with success defined as a drop in Eckardt score to 3 or less at 1 year post treatment.

"In contrast, in type II, the success rate for dilation was significantly higher than that of myotomy, ... with 100% treatment success in the [dilation] group, compared to 93% in the [myotomy] group," the authors wrote (P less than .05).

Type III patients, in contrast, had overall lower success rates, with 86% for myotomy and 40% for dilation (the difference between the groups could not be assessed for significance because there were too few patients with type III achalasia).

In any case, "irrespective of treatment arm, success rate after a mean follow-up of 43 months was significantly higher in patients with type II compared to type I (P less than .01) and type III (P less than .001)," the researchers wrote.

The authors conceded that the manometry subtype classification system developed by Pandolfino was designed for use with high-resolution manometry instead of the conventional manometry used in their study.

They noted, however, that at least one study has found 100% agreement between the classification of subtypes based on conventional pressure line tracings versus high-resolution manometry plots, and "our three patient groups were similar to those reported by Pandolfino, in terms of both clinical features and outcome after therapy."

Indeed, "based on our findings, we conclude that when a graded distension protocol allowing redilation is used, pneumatic dilation and laparoscopic Heller myotomy are both appropriate treatment options for type I and type II achalasia, at least until longer follow-up data are available," the authors concluded.

The researchers stated that they had no competing interests to disclose in relation to this study. One of the authors disclosed being funded by a grant from the Flemish government.

Proton pump inhibitor use was associated with a greater than 75% reduction in the risk of neoplastic progression in Barrett’s esophagus.

Indeed, despite the "considerable costs" of these drugs, "prolonged PPI use is ... justified and feasible in Barrett’s patients and should be strongly recommended, in particular in guidelines," concluded Dr. Florine Kastelein in the April 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.11.014).

In what they called "the first methodological[ly] sound prospective study which shows that PPIs strongly reduce the risk of neoplastic progression in BE," Dr. Kastelein of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues looked at 540 patients with known or newly diagnosed endoscopic Barrett’s esophagus (BE) confirmed by intestinal metaplasia.

Patients had a median age of 60.5 years at inclusion and were followed for a median of 5.2 years; 71% were male.

All patients were recruited from multiple academic and regional hospitals across the Netherlands, and patients were excluded if they had Barrett’s esophagus shorter than 2 cm, prior antireflux surgery, or a history of high-grade dysplasia or esophageal adenocarcinoma.

Patients with neoplastic progression found within the first 9 months after study inclusion also were ultimately excluded "since high-grade dysplasia or esophageal adenocarcinoma may be missed at index endoscopy in these patients," the investigators said.

Surveillance was performed according to the guidelines of the American College of Gastroenterology, such that patients without dysplasia underwent gastroscopy with biopsy sampling every 3 years and patients with low-grade dysplasia underwent it every year.

Overall, at inclusion in the study, 462 (85%) patients had used a PPI for a median duration of 4.0 years.

Dr. Kastelien and her associates found that, during follow-up, 28 patients developed high-grade dysplasia and another 12 developed esophageal adenocarcinoma, for a combined annual incidence of 1.6%.

"PPI use at inclusion was associated with a reduced risk of neoplastic progression (hazard ratio, 0.43; 95% confidence interval: 0.21-0.88) and remained associated with a trend toward a protective effect after adjusting for age, gender, time of BE diagnosis, BE length, esophagitis histology, and use of other medications (HR, 0.47; 95% CI: 0.19-1.18)," the researchers wrote.

Moreover, among the 99% of patients who used a PPI at any time during follow-up (median, 5.1 years), time-dependent analysis revealed that PPI use was associated with a reduced risk of neoplastic progression (HR, 0.15; 95% CI: 0.06-0.40) and remained so after adjusting for age, gender, BE length, histology, baseline PPI use, and use of other medications (HR, 0.21; 95% CI: 0.07-0.66).

The authors found no significant difference between neoplastic progression and the various PPIs assessed in this study (including esomeprazole and pantoprazole as well as omeprazole, rabeprazole, and lansoprazole).

According to Dr. Kastelein and her associates, the study is actually limited by the incredibly high rate of compliance among its population.

"Despite the large sample size, only eight (2%) patients never used a PPI and 18 (3%) patients used a PPI during [only] a part of their follow-up period," they wrote.

"Although this reflects clinical practice in Western countries and is representative for a disease in which patients seek to avoid reflux symptoms, it limits the options for investigating the effect of PPIs," they added.

However, "because not all patients used PPIs throughout their entire follow-up period, we were able to perform time-dependent analyses."

Proton pump inhibitor use was associated with a greater than 75% reduction in the risk of neoplastic progression in Barrett’s esophagus.

Indeed, despite the "considerable costs" of these drugs, "prolonged PPI use is ... justified and feasible in Barrett’s patients and should be strongly recommended, in particular in guidelines," concluded Dr. Florine Kastelein in the April 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.11.014).

In what they called "the first methodological[ly] sound prospective study which shows that PPIs strongly reduce the risk of neoplastic progression in BE," Dr. Kastelein of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues looked at 540 patients with known or newly diagnosed endoscopic Barrett’s esophagus (BE) confirmed by intestinal metaplasia.

Patients had a median age of 60.5 years at inclusion and were followed for a median of 5.2 years; 71% were male.

All patients were recruited from multiple academic and regional hospitals across the Netherlands, and patients were excluded if they had Barrett’s esophagus shorter than 2 cm, prior antireflux surgery, or a history of high-grade dysplasia or esophageal adenocarcinoma.

Patients with neoplastic progression found within the first 9 months after study inclusion also were ultimately excluded "since high-grade dysplasia or esophageal adenocarcinoma may be missed at index endoscopy in these patients," the investigators said.

Surveillance was performed according to the guidelines of the American College of Gastroenterology, such that patients without dysplasia underwent gastroscopy with biopsy sampling every 3 years and patients with low-grade dysplasia underwent it every year.

Overall, at inclusion in the study, 462 (85%) patients had used a PPI for a median duration of 4.0 years.

Dr. Kastelien and her associates found that, during follow-up, 28 patients developed high-grade dysplasia and another 12 developed esophageal adenocarcinoma, for a combined annual incidence of 1.6%.

"PPI use at inclusion was associated with a reduced risk of neoplastic progression (hazard ratio, 0.43; 95% confidence interval: 0.21-0.88) and remained associated with a trend toward a protective effect after adjusting for age, gender, time of BE diagnosis, BE length, esophagitis histology, and use of other medications (HR, 0.47; 95% CI: 0.19-1.18)," the researchers wrote.

Moreover, among the 99% of patients who used a PPI at any time during follow-up (median, 5.1 years), time-dependent analysis revealed that PPI use was associated with a reduced risk of neoplastic progression (HR, 0.15; 95% CI: 0.06-0.40) and remained so after adjusting for age, gender, BE length, histology, baseline PPI use, and use of other medications (HR, 0.21; 95% CI: 0.07-0.66).

The authors found no significant difference between neoplastic progression and the various PPIs assessed in this study (including esomeprazole and pantoprazole as well as omeprazole, rabeprazole, and lansoprazole).

According to Dr. Kastelein and her associates, the study is actually limited by the incredibly high rate of compliance among its population.

"Despite the large sample size, only eight (2%) patients never used a PPI and 18 (3%) patients used a PPI during [only] a part of their follow-up period," they wrote.

"Although this reflects clinical practice in Western countries and is representative for a disease in which patients seek to avoid reflux symptoms, it limits the options for investigating the effect of PPIs," they added.

However, "because not all patients used PPIs throughout their entire follow-up period, we were able to perform time-dependent analyses."

Proton pump inhibitor use was associated with a greater than 75% reduction in the risk of neoplastic progression in Barrett’s esophagus.

Indeed, despite the "considerable costs" of these drugs, "prolonged PPI use is ... justified and feasible in Barrett’s patients and should be strongly recommended, in particular in guidelines," concluded Dr. Florine Kastelein in the April 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.11.014).

In what they called "the first methodological[ly] sound prospective study which shows that PPIs strongly reduce the risk of neoplastic progression in BE," Dr. Kastelein of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues looked at 540 patients with known or newly diagnosed endoscopic Barrett’s esophagus (BE) confirmed by intestinal metaplasia.

Patients had a median age of 60.5 years at inclusion and were followed for a median of 5.2 years; 71% were male.

All patients were recruited from multiple academic and regional hospitals across the Netherlands, and patients were excluded if they had Barrett’s esophagus shorter than 2 cm, prior antireflux surgery, or a history of high-grade dysplasia or esophageal adenocarcinoma.

Patients with neoplastic progression found within the first 9 months after study inclusion also were ultimately excluded "since high-grade dysplasia or esophageal adenocarcinoma may be missed at index endoscopy in these patients," the investigators said.

Surveillance was performed according to the guidelines of the American College of Gastroenterology, such that patients without dysplasia underwent gastroscopy with biopsy sampling every 3 years and patients with low-grade dysplasia underwent it every year.

Overall, at inclusion in the study, 462 (85%) patients had used a PPI for a median duration of 4.0 years.

Dr. Kastelien and her associates found that, during follow-up, 28 patients developed high-grade dysplasia and another 12 developed esophageal adenocarcinoma, for a combined annual incidence of 1.6%.

"PPI use at inclusion was associated with a reduced risk of neoplastic progression (hazard ratio, 0.43; 95% confidence interval: 0.21-0.88) and remained associated with a trend toward a protective effect after adjusting for age, gender, time of BE diagnosis, BE length, esophagitis histology, and use of other medications (HR, 0.47; 95% CI: 0.19-1.18)," the researchers wrote.

Moreover, among the 99% of patients who used a PPI at any time during follow-up (median, 5.1 years), time-dependent analysis revealed that PPI use was associated with a reduced risk of neoplastic progression (HR, 0.15; 95% CI: 0.06-0.40) and remained so after adjusting for age, gender, BE length, histology, baseline PPI use, and use of other medications (HR, 0.21; 95% CI: 0.07-0.66).

The authors found no significant difference between neoplastic progression and the various PPIs assessed in this study (including esomeprazole and pantoprazole as well as omeprazole, rabeprazole, and lansoprazole).

According to Dr. Kastelein and her associates, the study is actually limited by the incredibly high rate of compliance among its population.

"Despite the large sample size, only eight (2%) patients never used a PPI and 18 (3%) patients used a PPI during [only] a part of their follow-up period," they wrote.

"Although this reflects clinical practice in Western countries and is representative for a disease in which patients seek to avoid reflux symptoms, it limits the options for investigating the effect of PPIs," they added.

However, "because not all patients used PPIs throughout their entire follow-up period, we were able to perform time-dependent analyses."

A small, swallowed, laser imaging capsule provides full-thickness imaging of the upper gastrointestinal tract without biopsy, and is quicker and less invasive than traditional endoscopy, according to the Harvard University researchers who are developing it.

About the size of a large multivitamin pill, the transparent capsule generates a near-infrared beam that spins rapidly about its circumference during transit. Changes in the reflected light allow cross-sectional imaging of the esophagus in a few minutes. Sequential cross-sections can be compiled into three-dimensional models of the entire lumen (Nat. Med. 2013 Jan. 13 [doi: 10.1038/nm.3052]).

Courtesy Wellman Center for Photomedicine, Massachusetts General Hospital

"This system gives us a convenient way to screen for Barrett’s [esophagus] that doesn’t require patient sedation, a specialized setting and equipment, or a physician who has been trained in endoscopy. By showing the three-dimensional, microscopic structure of the esophageal lining, it reveals much more detail than can be seen with even high-resolution endoscopy. The images produced have been some of the best we have seen of the esophagus," investigator Dr. Guillermo Tearney, a Harvard Medical School pathology professor and the associate director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said in a statement.

The capsule is on a tether, which carries its fiber optic line and laser driveshaft and helps with positioning. The capsule is pulled up and out after use, and disinfected for the next patient.

In early testing, 15 cm of esophagus in seven healthy and six Barrett’s esophagus patients was imaged in a mean of 58 seconds; it took about 6 minutes to make two down- and two up-transits. The technique, dubbed tethered capsule endomicroscopy, clearly distinguished the cellular abnormalities of Barrett’s. Standard upper GI endoscopy takes about 90 minutes.

Courtesy Wellman Center for Photomedicine, Massachusetts General Hospital

"We originally were concerned that we might miss a lot of data because of the small size of the capsule, but we were surprised to find that, once the pill has been swallowed, it is firmly grasped by the esophagus, allowing complete microscopic imaging of the entire wall," Dr. Tearney said.

There were no complications, and 12 of the 13 subjects said they preferred the capsule to previous endoscopies.

"Because the tethered endomicroscopy pill traverses the gastrointestinal tract without visual guidance, the training required to conduct the procedure is minimal. This fact, combined with the brevity and ease with which the procedure is performed, will enable internal microscopic imaging in almost any health care setting, including in the office of the primary care physician," Dr. Tearney and his colleagues wrote in their paper.

The research was supported by grants from the National Institutes of Health. The researchers said they had no disclosures.

A small, swallowed, laser imaging capsule provides full-thickness imaging of the upper gastrointestinal tract without biopsy, and is quicker and less invasive than traditional endoscopy, according to the Harvard University researchers who are developing it.

About the size of a large multivitamin pill, the transparent capsule generates a near-infrared beam that spins rapidly about its circumference during transit. Changes in the reflected light allow cross-sectional imaging of the esophagus in a few minutes. Sequential cross-sections can be compiled into three-dimensional models of the entire lumen (Nat. Med. 2013 Jan. 13 [doi: 10.1038/nm.3052]).

Courtesy Wellman Center for Photomedicine, Massachusetts General Hospital

"This system gives us a convenient way to screen for Barrett’s [esophagus] that doesn’t require patient sedation, a specialized setting and equipment, or a physician who has been trained in endoscopy. By showing the three-dimensional, microscopic structure of the esophageal lining, it reveals much more detail than can be seen with even high-resolution endoscopy. The images produced have been some of the best we have seen of the esophagus," investigator Dr. Guillermo Tearney, a Harvard Medical School pathology professor and the associate director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said in a statement.

The capsule is on a tether, which carries its fiber optic line and laser driveshaft and helps with positioning. The capsule is pulled up and out after use, and disinfected for the next patient.

In early testing, 15 cm of esophagus in seven healthy and six Barrett’s esophagus patients was imaged in a mean of 58 seconds; it took about 6 minutes to make two down- and two up-transits. The technique, dubbed tethered capsule endomicroscopy, clearly distinguished the cellular abnormalities of Barrett’s. Standard upper GI endoscopy takes about 90 minutes.

Courtesy Wellman Center for Photomedicine, Massachusetts General Hospital

"We originally were concerned that we might miss a lot of data because of the small size of the capsule, but we were surprised to find that, once the pill has been swallowed, it is firmly grasped by the esophagus, allowing complete microscopic imaging of the entire wall," Dr. Tearney said.

There were no complications, and 12 of the 13 subjects said they preferred the capsule to previous endoscopies.

"Because the tethered endomicroscopy pill traverses the gastrointestinal tract without visual guidance, the training required to conduct the procedure is minimal. This fact, combined with the brevity and ease with which the procedure is performed, will enable internal microscopic imaging in almost any health care setting, including in the office of the primary care physician," Dr. Tearney and his colleagues wrote in their paper.

The research was supported by grants from the National Institutes of Health. The researchers said they had no disclosures.

A small, swallowed, laser imaging capsule provides full-thickness imaging of the upper gastrointestinal tract without biopsy, and is quicker and less invasive than traditional endoscopy, according to the Harvard University researchers who are developing it.

About the size of a large multivitamin pill, the transparent capsule generates a near-infrared beam that spins rapidly about its circumference during transit. Changes in the reflected light allow cross-sectional imaging of the esophagus in a few minutes. Sequential cross-sections can be compiled into three-dimensional models of the entire lumen (Nat. Med. 2013 Jan. 13 [doi: 10.1038/nm.3052]).

Courtesy Wellman Center for Photomedicine, Massachusetts General Hospital

"This system gives us a convenient way to screen for Barrett’s [esophagus] that doesn’t require patient sedation, a specialized setting and equipment, or a physician who has been trained in endoscopy. By showing the three-dimensional, microscopic structure of the esophageal lining, it reveals much more detail than can be seen with even high-resolution endoscopy. The images produced have been some of the best we have seen of the esophagus," investigator Dr. Guillermo Tearney, a Harvard Medical School pathology professor and the associate director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said in a statement.

The capsule is on a tether, which carries its fiber optic line and laser driveshaft and helps with positioning. The capsule is pulled up and out after use, and disinfected for the next patient.

In early testing, 15 cm of esophagus in seven healthy and six Barrett’s esophagus patients was imaged in a mean of 58 seconds; it took about 6 minutes to make two down- and two up-transits. The technique, dubbed tethered capsule endomicroscopy, clearly distinguished the cellular abnormalities of Barrett’s. Standard upper GI endoscopy takes about 90 minutes.

Courtesy Wellman Center for Photomedicine, Massachusetts General Hospital

"We originally were concerned that we might miss a lot of data because of the small size of the capsule, but we were surprised to find that, once the pill has been swallowed, it is firmly grasped by the esophagus, allowing complete microscopic imaging of the entire wall," Dr. Tearney said.

There were no complications, and 12 of the 13 subjects said they preferred the capsule to previous endoscopies.

"Because the tethered endomicroscopy pill traverses the gastrointestinal tract without visual guidance, the training required to conduct the procedure is minimal. This fact, combined with the brevity and ease with which the procedure is performed, will enable internal microscopic imaging in almost any health care setting, including in the office of the primary care physician," Dr. Tearney and his colleagues wrote in their paper.

The research was supported by grants from the National Institutes of Health. The researchers said they had no disclosures.

A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastric ulcers and treatment discontinuations than conventional enteric-coated aspirin in two pivotal phase III clinical trials reported at the annual scientific sessions of the American Heart Association.

The two double-blind, 6-month, multicenter, randomized phase III studies included 1,049 patients who had coronary heart disease and were taking aspirin for secondary cardiovascular prevention. Based upon the highly favorable results reported by Dr. David L. Whellan at the meeting as well as other evidence, the studies’ sponsor, Pozen, will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary prevention of cardiovascular events in the roughly 15% of patients at risk for aspirin-induced upper-GI adverse events.

Study participants were randomized to once-daily conventional enteric-coated aspirin at 325 mg or to the investigational tablet, known for now as PA32540. The primary endpoint – the 6-month rate of endoscopically confirmed gastric ulcers – occurred in 3.8% of the PA32540 group, compared with 8.7% of controls, in one 524-patient study and in 2.7% of the PA32540 group, versus 8.5% of controls, in the 525-patient second study. This corresponds to relative risk reductions of 56% and 68%, respectively, according to Dr. Whellan of Thomas Jefferson University, Philadelphia.

A key secondary endpoint was the 6-month treatment discontinuation rate as a result of dyspepsia, erosive gastritis, and other upper-GI adverse events. The combined rate in the two trials was 1.5% in the PA32540 group and 8.2% in patients on enteric-coated aspirin, for an 82% relative risk reduction.

The rate of discontinuation for any adverse events was 6.7% with PA32540 and 11.2% in controls. Since patient adherence to aspirin therapy saves lives, these are clinically important outcomes, he noted.

The rate of acute MI and other major adverse cardiovascular events was 1.7% in the PA32540 group and 2.5% in controls, a nonsignificant difference. The study wasn’t of sufficient size or duration to provide definitive evidence regarding this endpoint.

PA32540 is a once-daily tablet containing 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin. Pozen has announced that it is currently seeking strategic partners to help market the novel product on a wide scale at an affordable cost once PA32540 receives regulatory approval.

Dr. Whellan is a consultant to Pozen.

A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastric ulcers and treatment discontinuations than conventional enteric-coated aspirin in two pivotal phase III clinical trials reported at the annual scientific sessions of the American Heart Association.

The two double-blind, 6-month, multicenter, randomized phase III studies included 1,049 patients who had coronary heart disease and were taking aspirin for secondary cardiovascular prevention. Based upon the highly favorable results reported by Dr. David L. Whellan at the meeting as well as other evidence, the studies’ sponsor, Pozen, will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary prevention of cardiovascular events in the roughly 15% of patients at risk for aspirin-induced upper-GI adverse events.

Study participants were randomized to once-daily conventional enteric-coated aspirin at 325 mg or to the investigational tablet, known for now as PA32540. The primary endpoint – the 6-month rate of endoscopically confirmed gastric ulcers – occurred in 3.8% of the PA32540 group, compared with 8.7% of controls, in one 524-patient study and in 2.7% of the PA32540 group, versus 8.5% of controls, in the 525-patient second study. This corresponds to relative risk reductions of 56% and 68%, respectively, according to Dr. Whellan of Thomas Jefferson University, Philadelphia.

A key secondary endpoint was the 6-month treatment discontinuation rate as a result of dyspepsia, erosive gastritis, and other upper-GI adverse events. The combined rate in the two trials was 1.5% in the PA32540 group and 8.2% in patients on enteric-coated aspirin, for an 82% relative risk reduction.

The rate of discontinuation for any adverse events was 6.7% with PA32540 and 11.2% in controls. Since patient adherence to aspirin therapy saves lives, these are clinically important outcomes, he noted.

The rate of acute MI and other major adverse cardiovascular events was 1.7% in the PA32540 group and 2.5% in controls, a nonsignificant difference. The study wasn’t of sufficient size or duration to provide definitive evidence regarding this endpoint.

PA32540 is a once-daily tablet containing 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin. Pozen has announced that it is currently seeking strategic partners to help market the novel product on a wide scale at an affordable cost once PA32540 receives regulatory approval.

Dr. Whellan is a consultant to Pozen.

A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastric ulcers and treatment discontinuations than conventional enteric-coated aspirin in two pivotal phase III clinical trials reported at the annual scientific sessions of the American Heart Association.

The two double-blind, 6-month, multicenter, randomized phase III studies included 1,049 patients who had coronary heart disease and were taking aspirin for secondary cardiovascular prevention. Based upon the highly favorable results reported by Dr. David L. Whellan at the meeting as well as other evidence, the studies’ sponsor, Pozen, will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary prevention of cardiovascular events in the roughly 15% of patients at risk for aspirin-induced upper-GI adverse events.

Study participants were randomized to once-daily conventional enteric-coated aspirin at 325 mg or to the investigational tablet, known for now as PA32540. The primary endpoint – the 6-month rate of endoscopically confirmed gastric ulcers – occurred in 3.8% of the PA32540 group, compared with 8.7% of controls, in one 524-patient study and in 2.7% of the PA32540 group, versus 8.5% of controls, in the 525-patient second study. This corresponds to relative risk reductions of 56% and 68%, respectively, according to Dr. Whellan of Thomas Jefferson University, Philadelphia.

A key secondary endpoint was the 6-month treatment discontinuation rate as a result of dyspepsia, erosive gastritis, and other upper-GI adverse events. The combined rate in the two trials was 1.5% in the PA32540 group and 8.2% in patients on enteric-coated aspirin, for an 82% relative risk reduction.

The rate of discontinuation for any adverse events was 6.7% with PA32540 and 11.2% in controls. Since patient adherence to aspirin therapy saves lives, these are clinically important outcomes, he noted.

The rate of acute MI and other major adverse cardiovascular events was 1.7% in the PA32540 group and 2.5% in controls, a nonsignificant difference. The study wasn’t of sufficient size or duration to provide definitive evidence regarding this endpoint.

PA32540 is a once-daily tablet containing 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin. Pozen has announced that it is currently seeking strategic partners to help market the novel product on a wide scale at an affordable cost once PA32540 receives regulatory approval.

Dr. Whellan is a consultant to Pozen.