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Concurrent NSAID, PPI use tapers over long term
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.
Factors increasing the risk for upper GI complications in NSAID users include older age (>60-75 years); prior upper GI complications or symptomatic ulcers; and concurrent use of aspirin, other antithrombotics, or corticosteroids. If patients cannot be switched to a non-NSAID analgesic, strategies recommended to decrease GI risk include PPI (or misoprostol) cotherapy or substitution of a COX-2 selective NSAID. Patients at very high risk (e.g., recent ulcer bleeding) should receive a COX-2 selective NSAID plus PPI (or misoprostol).
However, multiple observational studies demonstrate that most NSAID users with GI risk factors do not receive protective therapy. Importantly, adherence to a PPI more than 80% of the time is associated with significantly fewer upper GI clinical events than adherence less than 80% and less than 20% of the time.
The study by Le Ray et al looks at a group of NSAID users in whom a decision to provide a PPI prescription has been made. Co-therapy was stopped in 23% of patients at 1 year and 32% at 2 years. The authors correctly indicate that these patients likely are at increased risk. However, the rate of discontinuation was less than might have been anticipated (and less than in another European study), and half those discontinuing PPIs resumed them within 6 months. Furthermore, a number of patients had characteristics for which protective therapy is not generally recommended: e.g., heart disease, rheumatoid arthritis, dyspepsia, and celecoxib use.
Finally, the authors report that lack of PPI prescription was associated with increased GI “adverse events,” “injury,” and “complications.” We should note, however, that these “events” were primarily symptoms rather than complications or clinical events.
Loren Laine, M.D., AGAF, is a professor of medicine (digestive diseases) at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He also is the current president of the AGA Institute. He reported that he is a member of data safety monitoring boards on studies sponsored by Bayer, Eisai, Merck.
Factors increasing the risk for upper GI complications in NSAID users include older age (>60-75 years); prior upper GI complications or symptomatic ulcers; and concurrent use of aspirin, other antithrombotics, or corticosteroids. If patients cannot be switched to a non-NSAID analgesic, strategies recommended to decrease GI risk include PPI (or misoprostol) cotherapy or substitution of a COX-2 selective NSAID. Patients at very high risk (e.g., recent ulcer bleeding) should receive a COX-2 selective NSAID plus PPI (or misoprostol).
However, multiple observational studies demonstrate that most NSAID users with GI risk factors do not receive protective therapy. Importantly, adherence to a PPI more than 80% of the time is associated with significantly fewer upper GI clinical events than adherence less than 80% and less than 20% of the time.
The study by Le Ray et al looks at a group of NSAID users in whom a decision to provide a PPI prescription has been made. Co-therapy was stopped in 23% of patients at 1 year and 32% at 2 years. The authors correctly indicate that these patients likely are at increased risk. However, the rate of discontinuation was less than might have been anticipated (and less than in another European study), and half those discontinuing PPIs resumed them within 6 months. Furthermore, a number of patients had characteristics for which protective therapy is not generally recommended: e.g., heart disease, rheumatoid arthritis, dyspepsia, and celecoxib use.
Finally, the authors report that lack of PPI prescription was associated with increased GI “adverse events,” “injury,” and “complications.” We should note, however, that these “events” were primarily symptoms rather than complications or clinical events.
Loren Laine, M.D., AGAF, is a professor of medicine (digestive diseases) at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He also is the current president of the AGA Institute. He reported that he is a member of data safety monitoring boards on studies sponsored by Bayer, Eisai, Merck.
Factors increasing the risk for upper GI complications in NSAID users include older age (>60-75 years); prior upper GI complications or symptomatic ulcers; and concurrent use of aspirin, other antithrombotics, or corticosteroids. If patients cannot be switched to a non-NSAID analgesic, strategies recommended to decrease GI risk include PPI (or misoprostol) cotherapy or substitution of a COX-2 selective NSAID. Patients at very high risk (e.g., recent ulcer bleeding) should receive a COX-2 selective NSAID plus PPI (or misoprostol).
However, multiple observational studies demonstrate that most NSAID users with GI risk factors do not receive protective therapy. Importantly, adherence to a PPI more than 80% of the time is associated with significantly fewer upper GI clinical events than adherence less than 80% and less than 20% of the time.
The study by Le Ray et al looks at a group of NSAID users in whom a decision to provide a PPI prescription has been made. Co-therapy was stopped in 23% of patients at 1 year and 32% at 2 years. The authors correctly indicate that these patients likely are at increased risk. However, the rate of discontinuation was less than might have been anticipated (and less than in another European study), and half those discontinuing PPIs resumed them within 6 months. Furthermore, a number of patients had characteristics for which protective therapy is not generally recommended: e.g., heart disease, rheumatoid arthritis, dyspepsia, and celecoxib use.
Finally, the authors report that lack of PPI prescription was associated with increased GI “adverse events,” “injury,” and “complications.” We should note, however, that these “events” were primarily symptoms rather than complications or clinical events.
Loren Laine, M.D., AGAF, is a professor of medicine (digestive diseases) at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He also is the current president of the AGA Institute. He reported that he is a member of data safety monitoring boards on studies sponsored by Bayer, Eisai, Merck.
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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Major finding: By 24 months after initial NSAID/PPI coprescription, the persistence probability of still having an active PPI prescription fell to 0.68 (95% CI, 0.66-0.70).
Data source: A retrospective, observational, longitudinal study of 1,856 patients in France at risk for GI events.
Disclosures: 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.
GI-friendly aspirin combo aces phase III trials
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.
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.
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.
AT THE INTERNATIONAL STROKE CONFERENCE
BMI does not influence PPI effectiveness in GERD or erosive esophagitis
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.
Major finding: BMI has no significant effect on resolving heartburn (OR = 1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis (OR = 1.01; 95% CI, 1.00-1.02; P = .23).
Data source: Two retrospective analyses of pooled data from several PPI studies conducted in patients with GERD (N = 704) and erosive esophagitis (N = 11,027).
Disclosures: The study was supported by AstraZeneca LP. The lead author receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda.
Manometric type II achalasia patients have best outcomes
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.
 |
| Dr. John Pandolfino |
Additionally, this paper also suggests that the achalasia subtypes developed using EPT can be assessed with conventional manometry, supporting the notion that this classification scheme is independent of the technology used. Achalasia subtypes have long been recognized with conventional manometry, however, the categories were somewhat vague and poorly described. Vigorous achalasia was a terminology utilized to describe atypical disorders of LES relaxation using the presence of some preserved peristalsis or simultaneous contractions to distinguish this pattern from classic achalasia (type I achalasia). Leveraging the detail from EPT, patients lumped into the “vigorous” category can now be separated into three distinct subtypes: type II (associated with panesophageal pressurization), type III (associated with spastic contractions) and esophagogastric junction (EGJ) outflow obstruction (associated with preserved peristalsis).
These subtypes are very different in terms of the prognosis and management. Type II patients have an excellent prognosis and while type III has a much poorer outcome due to the overlapping spastic features, which are difficult to treat. EGJ outflow obstruction is a unique diagnosis that can present as achalasia, but may also be associated with a subtle mechanical obstruction. Thus, defining these subtypes will alter management of patients with achalasia and these subtypes should not be overlooked in future research studies focused on achalasia pathogenesis and treatment.
John Pandolfino, M.D., AGAF, is a professor of medicine at the Feinberg School of Medicine at Northwestern University, Chicago. He is a consultant for Given Imaging, Sandhill Scientific, and Medical Measurement Systems. He is also a speaker for AstraZeneca and Given Imaging.
|
| Dr. John Pandolfino |
Additionally, this paper also suggests that the achalasia subtypes developed using EPT can be assessed with conventional manometry, supporting the notion that this classification scheme is independent of the technology used. Achalasia subtypes have long been recognized with conventional manometry, however, the categories were somewhat vague and poorly described. Vigorous achalasia was a terminology utilized to describe atypical disorders of LES relaxation using the presence of some preserved peristalsis or simultaneous contractions to distinguish this pattern from classic achalasia (type I achalasia). Leveraging the detail from EPT, patients lumped into the “vigorous” category can now be separated into three distinct subtypes: type II (associated with panesophageal pressurization), type III (associated with spastic contractions) and esophagogastric junction (EGJ) outflow obstruction (associated with preserved peristalsis).
These subtypes are very different in terms of the prognosis and management. Type II patients have an excellent prognosis and while type III has a much poorer outcome due to the overlapping spastic features, which are difficult to treat. EGJ outflow obstruction is a unique diagnosis that can present as achalasia, but may also be associated with a subtle mechanical obstruction. Thus, defining these subtypes will alter management of patients with achalasia and these subtypes should not be overlooked in future research studies focused on achalasia pathogenesis and treatment.
John Pandolfino, M.D., AGAF, is a professor of medicine at the Feinberg School of Medicine at Northwestern University, Chicago. He is a consultant for Given Imaging, Sandhill Scientific, and Medical Measurement Systems. He is also a speaker for AstraZeneca and Given Imaging.
|
| Dr. John Pandolfino |
Additionally, this paper also suggests that the achalasia subtypes developed using EPT can be assessed with conventional manometry, supporting the notion that this classification scheme is independent of the technology used. Achalasia subtypes have long been recognized with conventional manometry, however, the categories were somewhat vague and poorly described. Vigorous achalasia was a terminology utilized to describe atypical disorders of LES relaxation using the presence of some preserved peristalsis or simultaneous contractions to distinguish this pattern from classic achalasia (type I achalasia). Leveraging the detail from EPT, patients lumped into the “vigorous” category can now be separated into three distinct subtypes: type II (associated with panesophageal pressurization), type III (associated with spastic contractions) and esophagogastric junction (EGJ) outflow obstruction (associated with preserved peristalsis).
These subtypes are very different in terms of the prognosis and management. Type II patients have an excellent prognosis and while type III has a much poorer outcome due to the overlapping spastic features, which are difficult to treat. EGJ outflow obstruction is a unique diagnosis that can present as achalasia, but may also be associated with a subtle mechanical obstruction. Thus, defining these subtypes will alter management of patients with achalasia and these subtypes should not be overlooked in future research studies focused on achalasia pathogenesis and treatment.
John Pandolfino, M.D., AGAF, is a professor of medicine at the Feinberg School of Medicine at Northwestern University, Chicago. He is a consultant for Given Imaging, Sandhill Scientific, and Medical Measurement Systems. He is also a speaker for AstraZeneca and Given Imaging.
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.
FROM GASTROENTEROLOGY
Major finding: Patients with manometric type II achalasia have higher success rates after dilation (93%) as well as myotomy (100%) at 1 year, compared with patients who have subtypes I and III.
Data source: A total of 176 patients enrolled in the prospective, randomized, multicenter European Achalasia Trial.
Disclosures: 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.
PPIs lower progression risk in Barrett's esophagus
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."
 |
| Dr. Nicholas J. Shaheen |
Kastelein and colleagues provide the best data yet in support of this approach. PPI use in their observational study was associated with a substantial risk reduction in cancer and high-grade dysplasia, both at study enrollment and in follow-up.
This is far-from-perfect evidence of a protective effect of PPIs in Barrett’s. As the authors recognize, there are several substantial issues limiting the study’s generalizability. The few patients who were not on a PPI may differ substantially from the rest in multiple unmeasurable ways. Also, to the credit of the Dutch health care system, 99% of Barrett’s patients were on PPIs for at least part of the follow-up, and 97% of total follow-up time was spent on PPIs. Therefore, the investigators had few non-PPI years to assess. In fact, the entire study really hinges on 12 years of non-PPI follow-up in subjects destined to go on to high-grade dysplasia/cancer.
Despite these limitations, this prospective study is the best to date, and may be the best we see on this topic. Given the weight of the observational data supporting PPI use in Barrett’s, a randomized controlled trial of PPIs versus placebo as an antineoplastic measure in Barrett’s will not likely be undertaken. Given the risk-benefit ratio, we should continue to promote PPI use in our Barrett’s patients, while acknowledging the less-than-perfect evidence underpinning this recommendation.
Nicholas J. Shaheen, M.D., MPH, AGAF, is professor of medicine and epidemiology, director of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine, Chapel Hill. He receives or has received research funding from Takeda Pharmaceuticals, AstraZeneca, and Shire.
|
| Dr. Nicholas J. Shaheen |
Kastelein and colleagues provide the best data yet in support of this approach. PPI use in their observational study was associated with a substantial risk reduction in cancer and high-grade dysplasia, both at study enrollment and in follow-up.
This is far-from-perfect evidence of a protective effect of PPIs in Barrett’s. As the authors recognize, there are several substantial issues limiting the study’s generalizability. The few patients who were not on a PPI may differ substantially from the rest in multiple unmeasurable ways. Also, to the credit of the Dutch health care system, 99% of Barrett’s patients were on PPIs for at least part of the follow-up, and 97% of total follow-up time was spent on PPIs. Therefore, the investigators had few non-PPI years to assess. In fact, the entire study really hinges on 12 years of non-PPI follow-up in subjects destined to go on to high-grade dysplasia/cancer.
Despite these limitations, this prospective study is the best to date, and may be the best we see on this topic. Given the weight of the observational data supporting PPI use in Barrett’s, a randomized controlled trial of PPIs versus placebo as an antineoplastic measure in Barrett’s will not likely be undertaken. Given the risk-benefit ratio, we should continue to promote PPI use in our Barrett’s patients, while acknowledging the less-than-perfect evidence underpinning this recommendation.
Nicholas J. Shaheen, M.D., MPH, AGAF, is professor of medicine and epidemiology, director of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine, Chapel Hill. He receives or has received research funding from Takeda Pharmaceuticals, AstraZeneca, and Shire.
|
| Dr. Nicholas J. Shaheen |
Kastelein and colleagues provide the best data yet in support of this approach. PPI use in their observational study was associated with a substantial risk reduction in cancer and high-grade dysplasia, both at study enrollment and in follow-up.
This is far-from-perfect evidence of a protective effect of PPIs in Barrett’s. As the authors recognize, there are several substantial issues limiting the study’s generalizability. The few patients who were not on a PPI may differ substantially from the rest in multiple unmeasurable ways. Also, to the credit of the Dutch health care system, 99% of Barrett’s patients were on PPIs for at least part of the follow-up, and 97% of total follow-up time was spent on PPIs. Therefore, the investigators had few non-PPI years to assess. In fact, the entire study really hinges on 12 years of non-PPI follow-up in subjects destined to go on to high-grade dysplasia/cancer.
Despite these limitations, this prospective study is the best to date, and may be the best we see on this topic. Given the weight of the observational data supporting PPI use in Barrett’s, a randomized controlled trial of PPIs versus placebo as an antineoplastic measure in Barrett’s will not likely be undertaken. Given the risk-benefit ratio, we should continue to promote PPI use in our Barrett’s patients, while acknowledging the less-than-perfect evidence underpinning this recommendation.
Nicholas J. Shaheen, M.D., MPH, AGAF, is professor of medicine and epidemiology, director of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine, Chapel Hill. He receives or has received research funding from Takeda Pharmaceuticals, AstraZeneca, and Shire.
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."
Major finding: In Barrett’s esophagus, use of proton pump inhibitors was associated with a hazard ratio of 0.21 for neoplastic progression.
Data source: A multicenter, prospective cohort study of 540 patients with known or newly diagnosed Barrett’s esophagus.
Disclosures: None of the authors disclosed any conflicts of interest related to this article. No funding was reported.
Laser pill has potential benefits over upper GI endoscopy
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]).
"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.
"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]).
"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.
"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]).
"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.
"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.
FROM NATURE MEDICINE
Major Finding: In early testing, 15 cm of esophagus was imaged in a mean of 58 seconds and clearly distinguished the cellular abnormalities of Barrett’s esophagus; it took about 6 minutes to make two down- and two up-transits.
Data Source: A pilot study to image the esophagus in seven healthy patients and six with Barrett’s esophagus.
Disclosures: The research was supported by grants from the National Institutes of Health. The investigators said they had no disclosures.
GI-friendly aspirin product performs well in phase III
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.
AT THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: An investigational combination of 325 mg of pH-sensitive aspirin and 40 mg of immediate-release omeprazole layered in a coordinated-delivery tablet resulted in an endoscopically confirmed gastric ulcer rate of 3.2% compared with 8.6% with 325 mg of enteric-coated aspirin once daily in two trials totaling 1,049 patients.
Data Source: The two randomized phase III trials of PA32540 were double-blind, multicenter, and 6 months in duration.
Disclosures: The pivotal trials were sponsored by Pozen. The presenter is a consultant to the company.
Manometry, esophagram combo detects achalasia posttreatment problems
High-resolution manometry with esophageal pressure topography is known to improve the accuracy of manometry for detecting achalasia and defined clinically relevant subtypes prior to treatment, but new data demonstrate that the procedure also is useful for evaluating treatment efficacy.
In a study of 31 men and 19 women aged 20-79 years, resolution of the achalasia pattern on high-resolution manometry with esophageal pressure topography (HRM-EPT) after treatment was associated with symptom improvement and reduced bolus retention, reported Dr. Frédéric Nicodème of Northwestern University, Chicago, and his colleagues.
Video source: American Gastroenterological Association's YouTube Channel
Study participants included one cohort of 25 patients who underwent endoscopy, HRM, timed barium esophagram (TBE) following a 200-mL barium swallow, and symptom assessment before treatment, and a second cohort of 25 treated patients who had pretreatment type 1 or 2 achalasia and who were undergoing a posttreatment study protocol including HRM, TBE, endoscopy, and symptom assessment. The investigators assessed dysphagia, regurgitation, retrosternal pain, and weight loss and used them to calculate an Eckardt score (ES) for both cohorts.
In the untreated cohort, which included 10 patients with type 1 achalasia and 15 with type 2 achalasia, the key EPT metric of integrated relaxation pressure (IRP) was significantly greater in the type 2 patients, as was the nadir-relaxation pressure. No differences were seen based on disease type with respect to resting esophagogastric junction (EGJ) pressure, barium column height, barium column width, or ES (Clin. Gastroenterol. Hepatol. 2012 Oct. 12 [doi: 10.1016/j.cgh.2012.10.015]).
No correlation was found between TBE column height at 5 minutes and IRP, resting EGJ pressure, nadir-EGJ relaxation pressure, or ES, and no correlation was seen between ES and IRP, resting EGJ pressure, or nadir-EGJ relaxation pressure.
In the posttreatment cohort, 10 patients, including 6 with type 1 disease and 4 with type 2 disease, had EPT findings of persistent achalasia pattern, and 15 had resolution of the achalasia pattern. Of these 15 patients, 8 converted to absent peristalsis and 7 to weak peristalsis.
"The IRP, resting EGJ pressure, and nadir-EGJ were all significantly correlated with posttreatment ES," the investigators noted.
Furthermore, TBE column height at 5 minutes, IRP, and ES were significantly lower in patients with resolved achalasia patterns on HRM than in those with a persistent achalasia pattern; the subgroup of 7 patients with weak peristalsis appeared to have the best outcome.
"The median TBE column height at 5 minutes was significantly lower [in those with weak peristalsis] than the three other groups, and ES showed a trend toward a lower value compared to the other 3 groups," they explained.
No significant correlations between TBE column height at 5 minutes and resting EGJ pressure or nadir-EGJ relaxation pressure were noted in the posttreatment patients. Only the IRP showed a weak correlation.
"The correlation between TBE column height at 5 minutes and ES after treatment was also not significant. However, the median TBE column height at 5 minutes for patients with an ES of 3 or greater was significantly greater than that for patients with an ES less than 3," they wrote.
"Our findings suggest that resolution of the achalasia pattern on EPT after treatment was associated with an improvement in symptoms and reduced bolus retention. Although the IRP was not strongly linearly correlated with symptom severity, when analyzed dichotomously patients with an IRP greater than or equal to 15 mm Hg had worse symptom scores and greater bolus retention on TBE compared to those with normal IRP values," the investigators wrote.
In contrast, no EPT pattern or metric, and no TBE variable predicted symptom severity in the untreated cohort, and barium height on TBE did not distinguish achalasia EPT subtypes, they noted.
"These findings suggest that in addition to its proven utility in detecting pretreatment achalasia, EPT also has utility in the management of posttreatment achalasia that can complement TBE," they said.
Although TBE did not distinguish disease subtypes, it does complement EPT, especially when the disease has progressed to an anatomic-dominant disorder, they said. Additional studies in larger series of patients are needed before and after therapy to confidently establish the relative merits of each evaluation with respect to the prediction of long-term outcomes and cost-effectiveness, they said.
This study was supported by the Public Health Service. The authors reported having no disclosures.
Most patients with achalasia do well in the postoperative period after either pneumatic dilation (PD) or laparoscopic surgical myotomy, with an initial success rate as high as 90% after 2 years. However, predicting failure based on symptom recurrence is problematic, as symptoms are often underreported or absent due to esophageal dilation or impaired esophageal sensation. Thus, a strategy of avoiding esophageal decompensation due to delayed diagnosis cannot solely rely on patient report of symptom recurrence. Objective testing by barium esophagram or esophageal manometry may be needed.
 |
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This study adds new knowledge regarding the benefit of high-resolution manometry (HRM) in the management of posttreatment achalasia. The novelty of the study is in its use of timed barium esophagram (TBE), HRM, and symptoms in a group of patients with achalasia pre- and posttherapy. TBE was previously advocated as the objective test of choice; however, this study suggests that TBE and HRM may be complementary in this regard.
What is clear from this report as well as others regarding objective testing in achalasia is that patients’ symptoms alone are a poor marker of esophageal emptying. Posttherapy testing with HRM and/or TBE with special emphasis on bolus emptying should be employed in order to avoid long-term complications with achalasia. The choice between the tests may depend on the expertise and availability of each of the proposed test modalities.
Dr. Vaezi is clinical director of the division of gastroenterology, hepatology, and nutrition, and director of the Center for Swallowing and Esophageal Disorders and Clinical Research at Vanderbilt University Medical Center, Nashville, Tenn. He said he had no conflicts of interest to disclose.
Most patients with achalasia do well in the postoperative period after either pneumatic dilation (PD) or laparoscopic surgical myotomy, with an initial success rate as high as 90% after 2 years. However, predicting failure based on symptom recurrence is problematic, as symptoms are often underreported or absent due to esophageal dilation or impaired esophageal sensation. Thus, a strategy of avoiding esophageal decompensation due to delayed diagnosis cannot solely rely on patient report of symptom recurrence. Objective testing by barium esophagram or esophageal manometry may be needed.
|
|
This study adds new knowledge regarding the benefit of high-resolution manometry (HRM) in the management of posttreatment achalasia. The novelty of the study is in its use of timed barium esophagram (TBE), HRM, and symptoms in a group of patients with achalasia pre- and posttherapy. TBE was previously advocated as the objective test of choice; however, this study suggests that TBE and HRM may be complementary in this regard.
What is clear from this report as well as others regarding objective testing in achalasia is that patients’ symptoms alone are a poor marker of esophageal emptying. Posttherapy testing with HRM and/or TBE with special emphasis on bolus emptying should be employed in order to avoid long-term complications with achalasia. The choice between the tests may depend on the expertise and availability of each of the proposed test modalities.
Dr. Vaezi is clinical director of the division of gastroenterology, hepatology, and nutrition, and director of the Center for Swallowing and Esophageal Disorders and Clinical Research at Vanderbilt University Medical Center, Nashville, Tenn. He said he had no conflicts of interest to disclose.
Most patients with achalasia do well in the postoperative period after either pneumatic dilation (PD) or laparoscopic surgical myotomy, with an initial success rate as high as 90% after 2 years. However, predicting failure based on symptom recurrence is problematic, as symptoms are often underreported or absent due to esophageal dilation or impaired esophageal sensation. Thus, a strategy of avoiding esophageal decompensation due to delayed diagnosis cannot solely rely on patient report of symptom recurrence. Objective testing by barium esophagram or esophageal manometry may be needed.
|
|
This study adds new knowledge regarding the benefit of high-resolution manometry (HRM) in the management of posttreatment achalasia. The novelty of the study is in its use of timed barium esophagram (TBE), HRM, and symptoms in a group of patients with achalasia pre- and posttherapy. TBE was previously advocated as the objective test of choice; however, this study suggests that TBE and HRM may be complementary in this regard.
What is clear from this report as well as others regarding objective testing in achalasia is that patients’ symptoms alone are a poor marker of esophageal emptying. Posttherapy testing with HRM and/or TBE with special emphasis on bolus emptying should be employed in order to avoid long-term complications with achalasia. The choice between the tests may depend on the expertise and availability of each of the proposed test modalities.
Dr. Vaezi is clinical director of the division of gastroenterology, hepatology, and nutrition, and director of the Center for Swallowing and Esophageal Disorders and Clinical Research at Vanderbilt University Medical Center, Nashville, Tenn. He said he had no conflicts of interest to disclose.
High-resolution manometry with esophageal pressure topography is known to improve the accuracy of manometry for detecting achalasia and defined clinically relevant subtypes prior to treatment, but new data demonstrate that the procedure also is useful for evaluating treatment efficacy.
In a study of 31 men and 19 women aged 20-79 years, resolution of the achalasia pattern on high-resolution manometry with esophageal pressure topography (HRM-EPT) after treatment was associated with symptom improvement and reduced bolus retention, reported Dr. Frédéric Nicodème of Northwestern University, Chicago, and his colleagues.
Video source: American Gastroenterological Association's YouTube Channel
Study participants included one cohort of 25 patients who underwent endoscopy, HRM, timed barium esophagram (TBE) following a 200-mL barium swallow, and symptom assessment before treatment, and a second cohort of 25 treated patients who had pretreatment type 1 or 2 achalasia and who were undergoing a posttreatment study protocol including HRM, TBE, endoscopy, and symptom assessment. The investigators assessed dysphagia, regurgitation, retrosternal pain, and weight loss and used them to calculate an Eckardt score (ES) for both cohorts.
In the untreated cohort, which included 10 patients with type 1 achalasia and 15 with type 2 achalasia, the key EPT metric of integrated relaxation pressure (IRP) was significantly greater in the type 2 patients, as was the nadir-relaxation pressure. No differences were seen based on disease type with respect to resting esophagogastric junction (EGJ) pressure, barium column height, barium column width, or ES (Clin. Gastroenterol. Hepatol. 2012 Oct. 12 [doi: 10.1016/j.cgh.2012.10.015]).
No correlation was found between TBE column height at 5 minutes and IRP, resting EGJ pressure, nadir-EGJ relaxation pressure, or ES, and no correlation was seen between ES and IRP, resting EGJ pressure, or nadir-EGJ relaxation pressure.
In the posttreatment cohort, 10 patients, including 6 with type 1 disease and 4 with type 2 disease, had EPT findings of persistent achalasia pattern, and 15 had resolution of the achalasia pattern. Of these 15 patients, 8 converted to absent peristalsis and 7 to weak peristalsis.
"The IRP, resting EGJ pressure, and nadir-EGJ were all significantly correlated with posttreatment ES," the investigators noted.
Furthermore, TBE column height at 5 minutes, IRP, and ES were significantly lower in patients with resolved achalasia patterns on HRM than in those with a persistent achalasia pattern; the subgroup of 7 patients with weak peristalsis appeared to have the best outcome.
"The median TBE column height at 5 minutes was significantly lower [in those with weak peristalsis] than the three other groups, and ES showed a trend toward a lower value compared to the other 3 groups," they explained.
No significant correlations between TBE column height at 5 minutes and resting EGJ pressure or nadir-EGJ relaxation pressure were noted in the posttreatment patients. Only the IRP showed a weak correlation.
"The correlation between TBE column height at 5 minutes and ES after treatment was also not significant. However, the median TBE column height at 5 minutes for patients with an ES of 3 or greater was significantly greater than that for patients with an ES less than 3," they wrote.
"Our findings suggest that resolution of the achalasia pattern on EPT after treatment was associated with an improvement in symptoms and reduced bolus retention. Although the IRP was not strongly linearly correlated with symptom severity, when analyzed dichotomously patients with an IRP greater than or equal to 15 mm Hg had worse symptom scores and greater bolus retention on TBE compared to those with normal IRP values," the investigators wrote.
In contrast, no EPT pattern or metric, and no TBE variable predicted symptom severity in the untreated cohort, and barium height on TBE did not distinguish achalasia EPT subtypes, they noted.
"These findings suggest that in addition to its proven utility in detecting pretreatment achalasia, EPT also has utility in the management of posttreatment achalasia that can complement TBE," they said.
Although TBE did not distinguish disease subtypes, it does complement EPT, especially when the disease has progressed to an anatomic-dominant disorder, they said. Additional studies in larger series of patients are needed before and after therapy to confidently establish the relative merits of each evaluation with respect to the prediction of long-term outcomes and cost-effectiveness, they said.
This study was supported by the Public Health Service. The authors reported having no disclosures.
High-resolution manometry with esophageal pressure topography is known to improve the accuracy of manometry for detecting achalasia and defined clinically relevant subtypes prior to treatment, but new data demonstrate that the procedure also is useful for evaluating treatment efficacy.
In a study of 31 men and 19 women aged 20-79 years, resolution of the achalasia pattern on high-resolution manometry with esophageal pressure topography (HRM-EPT) after treatment was associated with symptom improvement and reduced bolus retention, reported Dr. Frédéric Nicodème of Northwestern University, Chicago, and his colleagues.
Video source: American Gastroenterological Association's YouTube Channel
Study participants included one cohort of 25 patients who underwent endoscopy, HRM, timed barium esophagram (TBE) following a 200-mL barium swallow, and symptom assessment before treatment, and a second cohort of 25 treated patients who had pretreatment type 1 or 2 achalasia and who were undergoing a posttreatment study protocol including HRM, TBE, endoscopy, and symptom assessment. The investigators assessed dysphagia, regurgitation, retrosternal pain, and weight loss and used them to calculate an Eckardt score (ES) for both cohorts.
In the untreated cohort, which included 10 patients with type 1 achalasia and 15 with type 2 achalasia, the key EPT metric of integrated relaxation pressure (IRP) was significantly greater in the type 2 patients, as was the nadir-relaxation pressure. No differences were seen based on disease type with respect to resting esophagogastric junction (EGJ) pressure, barium column height, barium column width, or ES (Clin. Gastroenterol. Hepatol. 2012 Oct. 12 [doi: 10.1016/j.cgh.2012.10.015]).
No correlation was found between TBE column height at 5 minutes and IRP, resting EGJ pressure, nadir-EGJ relaxation pressure, or ES, and no correlation was seen between ES and IRP, resting EGJ pressure, or nadir-EGJ relaxation pressure.
In the posttreatment cohort, 10 patients, including 6 with type 1 disease and 4 with type 2 disease, had EPT findings of persistent achalasia pattern, and 15 had resolution of the achalasia pattern. Of these 15 patients, 8 converted to absent peristalsis and 7 to weak peristalsis.
"The IRP, resting EGJ pressure, and nadir-EGJ were all significantly correlated with posttreatment ES," the investigators noted.
Furthermore, TBE column height at 5 minutes, IRP, and ES were significantly lower in patients with resolved achalasia patterns on HRM than in those with a persistent achalasia pattern; the subgroup of 7 patients with weak peristalsis appeared to have the best outcome.
"The median TBE column height at 5 minutes was significantly lower [in those with weak peristalsis] than the three other groups, and ES showed a trend toward a lower value compared to the other 3 groups," they explained.
No significant correlations between TBE column height at 5 minutes and resting EGJ pressure or nadir-EGJ relaxation pressure were noted in the posttreatment patients. Only the IRP showed a weak correlation.
"The correlation between TBE column height at 5 minutes and ES after treatment was also not significant. However, the median TBE column height at 5 minutes for patients with an ES of 3 or greater was significantly greater than that for patients with an ES less than 3," they wrote.
"Our findings suggest that resolution of the achalasia pattern on EPT after treatment was associated with an improvement in symptoms and reduced bolus retention. Although the IRP was not strongly linearly correlated with symptom severity, when analyzed dichotomously patients with an IRP greater than or equal to 15 mm Hg had worse symptom scores and greater bolus retention on TBE compared to those with normal IRP values," the investigators wrote.
In contrast, no EPT pattern or metric, and no TBE variable predicted symptom severity in the untreated cohort, and barium height on TBE did not distinguish achalasia EPT subtypes, they noted.
"These findings suggest that in addition to its proven utility in detecting pretreatment achalasia, EPT also has utility in the management of posttreatment achalasia that can complement TBE," they said.
Although TBE did not distinguish disease subtypes, it does complement EPT, especially when the disease has progressed to an anatomic-dominant disorder, they said. Additional studies in larger series of patients are needed before and after therapy to confidently establish the relative merits of each evaluation with respect to the prediction of long-term outcomes and cost-effectiveness, they said.
This study was supported by the Public Health Service. The authors reported having no disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Major Finding: In a study of 31 men and 19 women aged 20-79 years, resolution of the achalasia pattern on HRM-EPT after treatment was associated with symptom improvement and reduced bolus retention.
Data Source: A prospective study of 50 achalasia patients.
Disclosures: This study was supported by the Public Health Service. The authors reported having no disclosures.
Scoring tool targets hospitalized patients needing acid suppressants
A scoring system based on demographics and comorbidities predicted which hospitalized patients were at risk for nosocomial gastrointestinal bleeding.
Used as a guideline for administering acid suppressors, the system found that treating fewer than 100 high-risk patients would prevent one case of bleeding, Dr. Shoshana Herzig and her colleagues wrote in the January online issue of General Internal Medicine (2013 [doi:10.1007/s11606-012-2296-x]).
"This scoring system allows identification of subsets of patients in whom the risk of nosocomial gastrointestinal bleeding may be higher enough to warrant the use of prophylactic acid-suppressive medication, in the absence of other indicators for use," said Dr. Herzig of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, and her coauthors.
The model "allows for risk stratification of patients using readily available information, and can be used to guide more selective use of acid-suppressive medication in patients outside of the ICU," the investigators wrote. The investigators reviewed about 76,000 records of noncritically ill patients hospitalized for more than 3 days, from 2004 through 2007. Nosocomial gastrointestinal bleeding occurred in about 3% of the group.
The authors constructed the risk score by identifying several factors that could potentially affect bleeding, including age, sex, comorbid conditions, admission service, and the receipt of certain medications during hospitalization.
A multivariate analysis identified those factors that significantly correlated with gastrointestinal bleeding. These included:
• Age more than 60 years (odds ratio, 2.2).
• Male sex (OR, 1.6).
• Liver disease (OR, 2.1).
• Acute renal failure (OR, 1.9).
• Admission to a medical service (OR, 2.7).
• Prophylactic anticoagulation (OR, 1.7).
• Coagulotherapy without antiplatelet medication (OR, 2.6).
• Coagulotherapy with one antiplatelet agent (OR, 3.2).
• Coagulotherapy with dual antiplatelet agents (OR, 3.3).
Based on these factors, they constructed a points-based risk scoring system that significantly correlated with the incidence of gastrointestinal bleeding. Patients in the lowest-score quartile were at the least risk of bleeding (less than 0.3%), while those in the highest quartile had the highest risk (1.5%).
The number needed to treat (NNT) to prevent one bleed increased as the risk score increased. The NNT was 500 in patients whose score was at least 6, 179 in those whose score was at least 8, 95 in those whose score was at least 10 (moderate risk), and 48 in those whose score was at least 12 (high risk).
The patients’ mean age was 56 years, although the range was very wide (18-107 years); 40% were male. Most patients received an acid-suppressing medication (58%). Proton pump inhibitors were most commonly used (81%); 29% received a histamine-2 receptor antagonist.
"With further validation at other medical centers, this scoring system may help clinicians individualize the decision to prescribe acid-suppressive medication as prophylaxis," the authors said.
The study was funded by grants from the National Institute on Aging and the National Center for Research Resources. None of the authors reported any financial conflicts.
A scoring system based on demographics and comorbidities predicted which hospitalized patients were at risk for nosocomial gastrointestinal bleeding.
Used as a guideline for administering acid suppressors, the system found that treating fewer than 100 high-risk patients would prevent one case of bleeding, Dr. Shoshana Herzig and her colleagues wrote in the January online issue of General Internal Medicine (2013 [doi:10.1007/s11606-012-2296-x]).
"This scoring system allows identification of subsets of patients in whom the risk of nosocomial gastrointestinal bleeding may be higher enough to warrant the use of prophylactic acid-suppressive medication, in the absence of other indicators for use," said Dr. Herzig of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, and her coauthors.
The model "allows for risk stratification of patients using readily available information, and can be used to guide more selective use of acid-suppressive medication in patients outside of the ICU," the investigators wrote. The investigators reviewed about 76,000 records of noncritically ill patients hospitalized for more than 3 days, from 2004 through 2007. Nosocomial gastrointestinal bleeding occurred in about 3% of the group.
The authors constructed the risk score by identifying several factors that could potentially affect bleeding, including age, sex, comorbid conditions, admission service, and the receipt of certain medications during hospitalization.
A multivariate analysis identified those factors that significantly correlated with gastrointestinal bleeding. These included:
• Age more than 60 years (odds ratio, 2.2).
• Male sex (OR, 1.6).
• Liver disease (OR, 2.1).
• Acute renal failure (OR, 1.9).
• Admission to a medical service (OR, 2.7).
• Prophylactic anticoagulation (OR, 1.7).
• Coagulotherapy without antiplatelet medication (OR, 2.6).
• Coagulotherapy with one antiplatelet agent (OR, 3.2).
• Coagulotherapy with dual antiplatelet agents (OR, 3.3).
Based on these factors, they constructed a points-based risk scoring system that significantly correlated with the incidence of gastrointestinal bleeding. Patients in the lowest-score quartile were at the least risk of bleeding (less than 0.3%), while those in the highest quartile had the highest risk (1.5%).
The number needed to treat (NNT) to prevent one bleed increased as the risk score increased. The NNT was 500 in patients whose score was at least 6, 179 in those whose score was at least 8, 95 in those whose score was at least 10 (moderate risk), and 48 in those whose score was at least 12 (high risk).
The patients’ mean age was 56 years, although the range was very wide (18-107 years); 40% were male. Most patients received an acid-suppressing medication (58%). Proton pump inhibitors were most commonly used (81%); 29% received a histamine-2 receptor antagonist.
"With further validation at other medical centers, this scoring system may help clinicians individualize the decision to prescribe acid-suppressive medication as prophylaxis," the authors said.
The study was funded by grants from the National Institute on Aging and the National Center for Research Resources. None of the authors reported any financial conflicts.
A scoring system based on demographics and comorbidities predicted which hospitalized patients were at risk for nosocomial gastrointestinal bleeding.
Used as a guideline for administering acid suppressors, the system found that treating fewer than 100 high-risk patients would prevent one case of bleeding, Dr. Shoshana Herzig and her colleagues wrote in the January online issue of General Internal Medicine (2013 [doi:10.1007/s11606-012-2296-x]).
"This scoring system allows identification of subsets of patients in whom the risk of nosocomial gastrointestinal bleeding may be higher enough to warrant the use of prophylactic acid-suppressive medication, in the absence of other indicators for use," said Dr. Herzig of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, and her coauthors.
The model "allows for risk stratification of patients using readily available information, and can be used to guide more selective use of acid-suppressive medication in patients outside of the ICU," the investigators wrote. The investigators reviewed about 76,000 records of noncritically ill patients hospitalized for more than 3 days, from 2004 through 2007. Nosocomial gastrointestinal bleeding occurred in about 3% of the group.
The authors constructed the risk score by identifying several factors that could potentially affect bleeding, including age, sex, comorbid conditions, admission service, and the receipt of certain medications during hospitalization.
A multivariate analysis identified those factors that significantly correlated with gastrointestinal bleeding. These included:
• Age more than 60 years (odds ratio, 2.2).
• Male sex (OR, 1.6).
• Liver disease (OR, 2.1).
• Acute renal failure (OR, 1.9).
• Admission to a medical service (OR, 2.7).
• Prophylactic anticoagulation (OR, 1.7).
• Coagulotherapy without antiplatelet medication (OR, 2.6).
• Coagulotherapy with one antiplatelet agent (OR, 3.2).
• Coagulotherapy with dual antiplatelet agents (OR, 3.3).
Based on these factors, they constructed a points-based risk scoring system that significantly correlated with the incidence of gastrointestinal bleeding. Patients in the lowest-score quartile were at the least risk of bleeding (less than 0.3%), while those in the highest quartile had the highest risk (1.5%).
The number needed to treat (NNT) to prevent one bleed increased as the risk score increased. The NNT was 500 in patients whose score was at least 6, 179 in those whose score was at least 8, 95 in those whose score was at least 10 (moderate risk), and 48 in those whose score was at least 12 (high risk).
The patients’ mean age was 56 years, although the range was very wide (18-107 years); 40% were male. Most patients received an acid-suppressing medication (58%). Proton pump inhibitors were most commonly used (81%); 29% received a histamine-2 receptor antagonist.
"With further validation at other medical centers, this scoring system may help clinicians individualize the decision to prescribe acid-suppressive medication as prophylaxis," the authors said.
The study was funded by grants from the National Institute on Aging and the National Center for Research Resources. None of the authors reported any financial conflicts.
FROM GENERAL INTERNAL MEDICINE
Major Finding: Acid suppressants would prevent one nosocomial gastrointestinal bleed for every 48 high-risk patients and every 95 moderate-risk patients treated, a risk-scoring system showed.
Data Source: A retrospective chart study of more than 76,000 patients.
Disclosures: The study was funded by grants from the National Institute on Aging and the National Center for Research Resources. None of the authors reported having any financial conflicts.
Restrictive transfusion strategy superior for severe acute GI bleeding
For patients with severe acute GI bleeding, outcomes are significantly better when a restrictive transfusion strategy is used – limiting the hemoglobin threshold to 7 g/dL – rather than a liberal transfusion strategy allowing a 9 g/dL threshold, according to a report published online Jan. 2 in the New England Journal of Medicine.
In a single-center randomized controlled trial involving 889 patients, the restrictive transfusion strategy resulted in significantly lower mortality, lower rates of rebleeding, less frequent need for rescue therapy, fewer complications, and shorter hospitalizations than did the liberal transfusion strategy. "Our results suggest that in patients with acute GI bleeding, a strategy of not performing transfusion until the hemoglobin concentration falls below 7 g/dL is a safe and effective approach," said Dr. Càndid Villanueva of Hospital de Sant Pau, Barcelona, and his associates.
"Current international guidelines recommend decreasing the hemoglobin threshold level for transfusion ... from 10g/dL to 7 g/dL" in such patients, but these recommendations are based on trials involving critically ill patients with normovolemic anemia that did not include subjects with acute bleeding. "Transfusion requirements may be different for patients with acute hemorrhage due to factors such as hemodynamic instability or rapid onset of anemia" resulting from extremely low hemoglobin levels.
In particular, results of animal studies suggest that transfusion can be especially harmful in patients with bleeding from portal hypertension sources, "since restitution of blood volume after hemorrhage can lead to a rebound increase in portal pressure, which is associated with a risk of rebleeding," the investigators noted.
To examine the effects of different transfusion strategies in this setting, Dr. Villanueva and his colleagues enrolled adults who presented with hematemesis, melena, or both, randomly assigning 444 to receive restrictive transfusion (with a target range for the posttransfusion hemoglobin level of 7-9 g/dL) and 445 to receive liberal transfusion (with a target range of 9-11 g/dL).
The study protocol permitted transfusions to be administered at the discretion of the attending physician any time symptoms or signs of anemia developed, massive bleeding occurred, or surgical intervention was needed, as well as when hemoglobin levels dipped below the assigned threshold.
All the study subjects underwent emergency gastroscopy within 6 hours of presentation, with appropriate treatment when the source of the bleeding was identified. Diagnoses included peptic ulcer, esophageal varices, cirrhosis, portal hypertension, and nonvariceal lesions.
The primary outcome measure, mortality from any cause at 45 days, was significantly lower in the restrictive-strategy group (5%) than the liberal-strategy group (9%). Death resulted from uncontrolled bleeding in 0.7% vs 3.1% of the 2 groups, respectively, the researchers said (N. Engl. J. Med. 2013 Jan. 2 [doi:10.1056/NEJMoa1211801]).
The rate of rebleeding also was significantly lower with the restrictive strategy (10% vs. 16%), and length of hospital stay was significantly shorter. In addition, rescue therapy for esophageal varices with balloon tamponade or a transjugular intrahepatic portosystemic shunt was required less often in the restrictive-strategy group than in the liberal-strategy group, as was emergency surgery to control further bleeding from peptic ulcer.
The rate of overall complications was significantly lower with the restrictive strategy (40%) than with the liberal strategy (48%), as was the rate of serious adverse events. In addition, transfusion reactions and cardiac events such as pulmonary edema were more frequent with the liberal strategy.
"Our results are consistent with those from previous observational studies and randomized trials performed in other settings, which have shown that a restrictive transfusion strategy did not increase, and even decreased, the mortality observed with a liberal transfusion strategy," Dr. Villanueva and his associates said.
This important study "provides long-awaited evidence to guide practice and justify current recommendations for the management of upper GI bleeding," said Dr. Loren Laine.
A restrictive transfusion strategy reduced the relative risk of mortality at 45 days by 45%. Extrapolating the study findings, only 25 patients would have to be treated with a restrictive rather than a liberal transfusion strategy to avert one additional death.
Dr. Laine is at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Villanueva’s report (N. Engl. J. Med. 2013 Jan. 2 [doi:10.1056/NEJMe1212009]).
This important study "provides long-awaited evidence to guide practice and justify current recommendations for the management of upper GI bleeding," said Dr. Loren Laine.
A restrictive transfusion strategy reduced the relative risk of mortality at 45 days by 45%. Extrapolating the study findings, only 25 patients would have to be treated with a restrictive rather than a liberal transfusion strategy to avert one additional death.
Dr. Laine is at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Villanueva’s report (N. Engl. J. Med. 2013 Jan. 2 [doi:10.1056/NEJMe1212009]).
This important study "provides long-awaited evidence to guide practice and justify current recommendations for the management of upper GI bleeding," said Dr. Loren Laine.
A restrictive transfusion strategy reduced the relative risk of mortality at 45 days by 45%. Extrapolating the study findings, only 25 patients would have to be treated with a restrictive rather than a liberal transfusion strategy to avert one additional death.
Dr. Laine is at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Villanueva’s report (N. Engl. J. Med. 2013 Jan. 2 [doi:10.1056/NEJMe1212009]).
For patients with severe acute GI bleeding, outcomes are significantly better when a restrictive transfusion strategy is used – limiting the hemoglobin threshold to 7 g/dL – rather than a liberal transfusion strategy allowing a 9 g/dL threshold, according to a report published online Jan. 2 in the New England Journal of Medicine.
In a single-center randomized controlled trial involving 889 patients, the restrictive transfusion strategy resulted in significantly lower mortality, lower rates of rebleeding, less frequent need for rescue therapy, fewer complications, and shorter hospitalizations than did the liberal transfusion strategy. "Our results suggest that in patients with acute GI bleeding, a strategy of not performing transfusion until the hemoglobin concentration falls below 7 g/dL is a safe and effective approach," said Dr. Càndid Villanueva of Hospital de Sant Pau, Barcelona, and his associates.
"Current international guidelines recommend decreasing the hemoglobin threshold level for transfusion ... from 10g/dL to 7 g/dL" in such patients, but these recommendations are based on trials involving critically ill patients with normovolemic anemia that did not include subjects with acute bleeding. "Transfusion requirements may be different for patients with acute hemorrhage due to factors such as hemodynamic instability or rapid onset of anemia" resulting from extremely low hemoglobin levels.
In particular, results of animal studies suggest that transfusion can be especially harmful in patients with bleeding from portal hypertension sources, "since restitution of blood volume after hemorrhage can lead to a rebound increase in portal pressure, which is associated with a risk of rebleeding," the investigators noted.
To examine the effects of different transfusion strategies in this setting, Dr. Villanueva and his colleagues enrolled adults who presented with hematemesis, melena, or both, randomly assigning 444 to receive restrictive transfusion (with a target range for the posttransfusion hemoglobin level of 7-9 g/dL) and 445 to receive liberal transfusion (with a target range of 9-11 g/dL).
The study protocol permitted transfusions to be administered at the discretion of the attending physician any time symptoms or signs of anemia developed, massive bleeding occurred, or surgical intervention was needed, as well as when hemoglobin levels dipped below the assigned threshold.
All the study subjects underwent emergency gastroscopy within 6 hours of presentation, with appropriate treatment when the source of the bleeding was identified. Diagnoses included peptic ulcer, esophageal varices, cirrhosis, portal hypertension, and nonvariceal lesions.
The primary outcome measure, mortality from any cause at 45 days, was significantly lower in the restrictive-strategy group (5%) than the liberal-strategy group (9%). Death resulted from uncontrolled bleeding in 0.7% vs 3.1% of the 2 groups, respectively, the researchers said (N. Engl. J. Med. 2013 Jan. 2 [doi:10.1056/NEJMoa1211801]).
The rate of rebleeding also was significantly lower with the restrictive strategy (10% vs. 16%), and length of hospital stay was significantly shorter. In addition, rescue therapy for esophageal varices with balloon tamponade or a transjugular intrahepatic portosystemic shunt was required less often in the restrictive-strategy group than in the liberal-strategy group, as was emergency surgery to control further bleeding from peptic ulcer.
The rate of overall complications was significantly lower with the restrictive strategy (40%) than with the liberal strategy (48%), as was the rate of serious adverse events. In addition, transfusion reactions and cardiac events such as pulmonary edema were more frequent with the liberal strategy.
"Our results are consistent with those from previous observational studies and randomized trials performed in other settings, which have shown that a restrictive transfusion strategy did not increase, and even decreased, the mortality observed with a liberal transfusion strategy," Dr. Villanueva and his associates said.
For patients with severe acute GI bleeding, outcomes are significantly better when a restrictive transfusion strategy is used – limiting the hemoglobin threshold to 7 g/dL – rather than a liberal transfusion strategy allowing a 9 g/dL threshold, according to a report published online Jan. 2 in the New England Journal of Medicine.
In a single-center randomized controlled trial involving 889 patients, the restrictive transfusion strategy resulted in significantly lower mortality, lower rates of rebleeding, less frequent need for rescue therapy, fewer complications, and shorter hospitalizations than did the liberal transfusion strategy. "Our results suggest that in patients with acute GI bleeding, a strategy of not performing transfusion until the hemoglobin concentration falls below 7 g/dL is a safe and effective approach," said Dr. Càndid Villanueva of Hospital de Sant Pau, Barcelona, and his associates.
"Current international guidelines recommend decreasing the hemoglobin threshold level for transfusion ... from 10g/dL to 7 g/dL" in such patients, but these recommendations are based on trials involving critically ill patients with normovolemic anemia that did not include subjects with acute bleeding. "Transfusion requirements may be different for patients with acute hemorrhage due to factors such as hemodynamic instability or rapid onset of anemia" resulting from extremely low hemoglobin levels.
In particular, results of animal studies suggest that transfusion can be especially harmful in patients with bleeding from portal hypertension sources, "since restitution of blood volume after hemorrhage can lead to a rebound increase in portal pressure, which is associated with a risk of rebleeding," the investigators noted.
To examine the effects of different transfusion strategies in this setting, Dr. Villanueva and his colleagues enrolled adults who presented with hematemesis, melena, or both, randomly assigning 444 to receive restrictive transfusion (with a target range for the posttransfusion hemoglobin level of 7-9 g/dL) and 445 to receive liberal transfusion (with a target range of 9-11 g/dL).
The study protocol permitted transfusions to be administered at the discretion of the attending physician any time symptoms or signs of anemia developed, massive bleeding occurred, or surgical intervention was needed, as well as when hemoglobin levels dipped below the assigned threshold.
All the study subjects underwent emergency gastroscopy within 6 hours of presentation, with appropriate treatment when the source of the bleeding was identified. Diagnoses included peptic ulcer, esophageal varices, cirrhosis, portal hypertension, and nonvariceal lesions.
The primary outcome measure, mortality from any cause at 45 days, was significantly lower in the restrictive-strategy group (5%) than the liberal-strategy group (9%). Death resulted from uncontrolled bleeding in 0.7% vs 3.1% of the 2 groups, respectively, the researchers said (N. Engl. J. Med. 2013 Jan. 2 [doi:10.1056/NEJMoa1211801]).
The rate of rebleeding also was significantly lower with the restrictive strategy (10% vs. 16%), and length of hospital stay was significantly shorter. In addition, rescue therapy for esophageal varices with balloon tamponade or a transjugular intrahepatic portosystemic shunt was required less often in the restrictive-strategy group than in the liberal-strategy group, as was emergency surgery to control further bleeding from peptic ulcer.
The rate of overall complications was significantly lower with the restrictive strategy (40%) than with the liberal strategy (48%), as was the rate of serious adverse events. In addition, transfusion reactions and cardiac events such as pulmonary edema were more frequent with the liberal strategy.
"Our results are consistent with those from previous observational studies and randomized trials performed in other settings, which have shown that a restrictive transfusion strategy did not increase, and even decreased, the mortality observed with a liberal transfusion strategy," Dr. Villanueva and his associates said.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major Finding: Mortality from any cause at 45 days was significantly lower in the restrictive-strategy group (5%) than in the liberal-strategy group (9%).
Data Source: A single-center randomized controlled trial of 889 patients.
Disclosures: This study was supported in part by the Fundacio Investigacio Sant Pau. Dr. Villanueva reported no financial conflicts of interest; one of his associates reported ties to Sequana Medical.