Jan Gunnar Hatlebakk

Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole

Objective To assess the efficacy of omeprazole in patients presenting with troublesome reflux symptoms. Design Randomized, double-blind, parallel-group, placebo-controlled comparison. Subjects Patients were recruited using a symptom-based questionnaire for diagnosis of gastro-oesophageal reflux disease. Interventions After endoscopy, patients without endoscopie oesophagitis were randomized to omeprazole 20 mg (Ome20), omeprazole 10 mg (Ome10) or placebo once daily for 4 weeks (n = 261) and those with oesophagitis (except circumferential/ulcerative) were randomized to receive either Ome20 or Ome10 once daily for 4 weeks (n = 277). Patients not symptom-free at 4 weeks received open treatment with Ome20 once daily for a further 4 weeks. Those symptom-free at 4–8 weeks were followed up for 6 months off treatment, to see whether their symptoms recurred. Main outcome measure Complete upper Gl symptom relief during week 4 on Ome20 or Ome10 in patients with or without endoscopie oesophagitis. Results Forty one percent of all patients on Ome20 and 35% on Ome10 reported complete relief from upper Gl symptoms during week 4, whilst 73% of the patients on Ome20 and 62% on Ome10 obtained sufficient control. Complete relief during week 4 was reported by 19% of endoscopy-negative patients on placebo, and sufficient control by 35%. Endoscopie healing at 4 weeks occurred in 76% of oesophagitis patients on Ome20 and in 56% on Ome10. After 6 months off treatment, 90% of patients with oesophagitis and 75% of endoscopy-negative patients reported symptomatic relapse. Conclusion Both 10 mg and 20 mg of omeprazole gave effective relief of symptoms, although 20 mg gave superior healing in patients with oesophagitis. After cessation of treatment, symptomatic relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative patients.

Continued (5-year) followup of a randomized clinical study comparing antireflux surgery and omeprazole in gastroesophageal reflux disease1

BACKGROUND The efficacy of antireflux surgery (ARS) and proton pump inhibitor therapy in the control of gastroesophageal reflux disease is well established. A direct comparison between these therapies is warranted to assess the benefits of respective therapies. STUDY DESIGN There were 310 patients with erosive esophagitis enrolled in the trial. There were 155 patients randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. Because of various withdrawals during the study course, 122 patients originally having an antireflux operation completed the 5-year followup; the corresponding figure in the omeprazole group was 133. Symptoms, endoscopy, and quality-of-life questionnaires were used to document clinical outcomes. Treatment failure was defined to occur if at least one of the following criteria were fulfilled: Moderate or severe heartburn or acid regurgitation during the last 7 days before the respective visit; Esophagitis of at least grade 2; Moderate or severe dysphagia or odynophagia symptoms reported in combination with mild heartburn or regurgitation; If randomized to surgery and subsequently required omeprazole for more than 8 weeks to control symptoms, or having a reoperation; If randomized to omeprazole and considered by the responsible physician to require antireflux surgery to control symptoms; If randomized to omeprazole and the patient, for any reason, preferred antireflux surgery during the course of the study. Treatment failure was the primary outcomes variable. RESULTS When the time to treatment failure was analyzed by use of the intention to treat approach, applying the life table analysis technique, a highly significant difference between the two strategies was revealed (p < 0.001), with more treatment failures in patients who originally were randomized to omeprazole treatment. The protocol also allowed dose adjustment in patients allocated to omeprazole therapy to either 40 or 60 mg daily in case of symptom recurrence. The curves subsequently describing the failure rates still remained separated in favor of surgery, although the difference did not reach statistical significance (p = 0.088). Quality of life assessment revealed values within normal ranges in both therapy arms during the 5 years. CONCLUSIONS In this randomized multicenter trial with a 5-year followup, we found antireflux surgery to be more effective than omeprazole in controlling gastroesophageal reflux disease as measured by the treatment failure rates. But if the dose of omeprazole was adjusted in case of relapse, the two therapeutic strategies reached levels of efficacy that were not statistically different.

Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial.

CONTEXT Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. OBJECTIVE To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD. DESIGN, SETTING, AND PARTICIPANTS The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially responded to acid suppression. A total of 372 patients (esomeprazole, n = 192; LARS, n = 180) completed 5-year follow-up. Interventions Two hundred sixty-six patients were randomly assigned to receive esomeprazole, 20 to 40 mg/d, allowing for dose adjustments; 288 were randomly assigned to undergo LARS, of whom 248 actually underwent the operation. MAIN OUTCOME MEASURE Time to treatment failure (for LARS, defined as need for acid suppressive therapy; for esomeprazole, inadequate symptom control after dose adjustment), expressed as estimated remission rates and analyzed using the Kaplan-Meier method. RESULTS Estimated remission rates at 5 years were 92% (95% confidence interval [CI], 89%-96%) in the esomeprazole group and 85% (95% CI, 81%-90%) in the LARS group (log-rank P = .048). The difference between groups was no longer statistically significant following best-case scenario modeling of the effects of study dropout. The prevalence and severity of symptoms at 5 years in the esomeprazole and LARS groups, respectively, were 16% and 8% for heartburn (P = .14), 13% and 2% for acid regurgitation (P < .001), 5% and 11% for dysphagia (P < .001), 28% and 40% for bloating (P < .001), and 40% and 57% for flatulence (P < .001). Mortality during the study was low (4 deaths in the esomeprazole group and 1 death in the LARS group) and not attributed to treatment, and the percentages of patients reporting serious adverse events were similar in the esomeprazole group (24.1%) and in the LARS group (28.6%). CONCLUSION This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00251927.

Ineffective esophageal motility : the most common motility abnormality in patients with GERD-associated respiratory symptoms

ObjectiveThe association of gastroesophageal reflux disease (GERD) and respiratory symptoms is well known. The coexistence of ineffective esophageal motility (IEM, low-amplitude [<30 mm Hg] or nontransmitted contractions in ≥30% of 10 wet swallows in the distal esophagus) in patients with GERD has recently been demonstrated. Our aim was to determine the prevalence of IEM in patients with GERD-associated respiratory symptoms.MethodsManometry and pH studies of 98 consecutive patients with respiratory symptoms and abnormal reflux shown by pH-metry were reviewed. Symptoms were chronic cough (n = 43), asthma (n = 13), and laryngitis (n = 42). Sixty-six patients with heartburn with no extraesophageal manifestations were used as a control group. Total esophageal acid clearance (EAC) time was calculated for each patient.ResultsIEM was the most common motility abnormality seen in all groups of GERD patients. It was seen significantly more often in patients with chronic cough (41%) (p= 0.003) or asthma (53%) (p= 0.01), and numerically more often in patients with laryngitis (31%) than in patients with heartburn (19%). Diffuse esophageal spasm and nutcracker esophagus were rarely seen. Incidence of hypertensive or hypotensive lower esophageal sphincter was similar across all groups. The total EAC time was longer (median: 1.51 min/episode) (p= 0.01) in patients with GERD-associated respiratory symptoms than in patients with heartburn (median: 0.72 min/episode).ConclusionsIEM is the most prevalent motility abnormality in patients with GERD-associated respiratory symptoms. Coexistence of IEM with GER may place patients at high risk for respiratory symptoms due to the associated delayed esophageal acid clearance seen with this motility abnormality.

Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: a 3-year interim analysis of the LOTUS trial

Background: With the introduction of laparoscopic antireflux surgery (LARS) for gastro-oesophageal reflux disease (GORD) along with the increasing efficacy of modern medical treatment, a direct comparison is warranted. The 3-year interim results of a randomised study comparing both the efficacy and safety of LARS and esomeprazole (ESO) are reported. Methods: LOTUS is an open, parallel-group multicentre, randomised and controlled trial conducted in dedicated centres in 11 European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg once daily, which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan–Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol. Results: 554 patients were randomised, of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the intention to treat population, p = 0.25 (90% vs 95% per protocol). No major unexpected postoperative complications were experienced and ESO was well tolerated. However, postfundoplication complaints remain a problem after LARS. Conclusions: Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD.

Seven-year follow-up of a randomized clinical trial comparing proton-pump inhibition with surgical therapy for reflux oesophagitis.

This randomized clinical trial compared long‐term outcome after antireflux surgery with acid inhibition therapy in the treatment of chronic gastro‐oesophageal reflux disease (GORD).

Proton pump inhibitors: better acid suppression when taken before a meal than without a meal

Proton pump inhibitors including omeprazole and lansoprazole inhibit gastric acid secretion by selectively and non‐competitively inactivating the H+, K+ ATPase molecules of the parietal cell, but possibly only those that are actively secreting acid. This might imply that stimulation of acid secretion by a meal is necessary for optimal inhibition of gastric secretion.

Gastroesophageal reflux in morbidly obese patients treated with gastric banding or vertical banded gastroplasty

OBJECTIVE To compare gastric banding (GB) and vertical banded gastroplasty (VBG) with respect to postsurgical gastroesophageal reflux (GER) and to investigate the role of preexisting hiatus hernia. SUMMARY BACKGROUND DATA GB and VBG have for a long time been used in the treatment of morbidly obese patients. The introduction of laparoscopic techniques has renewed the interest in these operations. The long-term results after GB have, however, been poor. VBG was suggested to have antireflux properties because it involves repositioning and retaining the gastroesophageal junction within the abdomen and constructing an elongated intraabdominal tube. METHODS Forty-three morbidly obese patients accepted for GB or VBG were evaluated for GER before and at regular intervals after surgery. All patients were questioned about adverse symptoms and need for antireflux medication. Both before and after surgery, 24-hour pH measurement and upper gastrointestinal endoscopies were performed. RESULTS The prevalence of heartburn and acid regurgitation among patients treated with GB increased from 14% and 13% to 63% and 69%, respectively. Heartburn and acid regurgitation were present before surgery in 32% and 23% of patients treated with VBG, percentages unchanged by the procedure. The 24-hour reflux time increased significantly from 6.4% to 30.9% in patients treated with GB but was essentially unchanged in patients treated with VBG. The prevalence of esophagitis after GB and VBG was 75% and 20%. Acid inhibitors were needed in 81% of patients after GB and 29% of patients after VBG. CONCLUSIONS The prevalence of GER was unchanged by VBG, but VBG did not demonstrate antireflux properties. The incidence of GER increased markedly after GB.

Long-term management of gastro-oesophageal reflux disease with omeprazole or open antireflux surgery: results of a prospective, randomized clinical trial. The Nordic GORD Study Group.

BACKGROUND AND AIM The efficacy of antireflux surgery (ARS) and omeprazole treatment in the control of gastrooesophageal reflux disease (GORD) are well established. We have compared these two therapeutic options in a randomized, clinical trial. PATIENTS AND METHODS Three hundred and ten patients with erosive oesophagitis were enrolled into the trial. After a run-in period when all patients had < or = 40 mg of omeprazole daily to heal the oesophagitis and relieve symptoms, 155 patients were randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. One hundred and thirty-nine and 129 in the omeprazole and antireflux surgery groups, respectively, completed the 3-year follow-up. Symptoms, 24-h pH monitoring and endoscopy were used to document the outcome. Quality of life was evaluated by the psychological general well-being (PGWB) index and the gastrointestinal symptom rating scale (GSRS). RESULTS Analysis of time to treatment failure (defined as moderate to severe GORD symptoms for > or = 3 days during the last 7 days, oesophagitis or changed therapy) revealed a significant difference in favour of antireflux surgery (P = 0.0016). Seventeen patients originally submitted to antireflux surgery experienced symptom relapse alone, 14 had oesophagitis at endoscopy and another six had omeprazole for different reasons, leaving 97 patients in clinical remission after 3 years. The corresponding figures in the omeprazole arm were 50 relapses, 18 with oesophagitis, two had surgery, leaving 77 patients in remission. Allowing a dose adjustment in the case of relapse in those on omeprazole therapy to either 40 or 60 mg, the curves describing the failure rates were not significantly different from each other. Quality of life assessment showed a comparable outcome in the two study groups. CONCLUSION In this randomized multicentre trial we found antireflux surgery to be very efficacious in controlling GORD, a level of control which could also be achieved by omeprazole provided that advantage was taken of the opportunity of adjusting the dose.

Comparison of Outcomes Twelve Years After Antireflux Surgery or Omeprazole Maintenance Therapy for Reflux Esophagitis

BACKGROUND & AIMS It is important to evaluate the long-term effects of therapies for gastroesophageal reflux disease (GERD). In a 12-year study, we compared the effects of therapy with omeprazole with those of antireflux surgery. METHODS This open, parallel group study included 310 patients with esophagitis enrolled from outpatient clinics in Nordic countries. Of the 155 patients randomly assigned to each arm of the study, 154 received omeprazole (1 withdrew before therapy began), and 144 received surgery (11 withdrew before surgery). In patients who remained in remission after treatment, post-fundoplication complaints, other symptoms, and safety variables were assessed. RESULTS Of the patients enrolled in the study, 71 who were given omeprazole (46%) and 53 treated with surgery (37%) were followed for a 12-year follow-up period. At this time point, 53% of patients who underwent surgery remained in continuous remission, compared with 45% of patients given omeprazole with a dose adjustment (P = .022) and 40% without dose adjustment (P = .002). In addition, 38% of surgical patients required a change in therapeutic strategy (eg, to medical therapy or another operation), compared with 15% of those on omeprazole. Heartburn and regurgitation were significantly more common in patients given omeprazole, whereas dysphagia, rectal flatulence, and the inability to belch or vomit were significantly more common in surgical patients. The therapies were otherwise well-tolerated. CONCLUSIONS As long-term therapeutic strategies for chronic GERD, surgery and omeprazole are effective and well-tolerated. Antireflux surgery is superior to omeprazole in controlling overall disease manifestations, but post-fundoplication complaints continue after surgery.