Family Practice Vol. 17, No. 5, 401-404
© Oxford University Press 2000
High dose proton pump inhibitor response as an initial strategy for a clinical diagnosis of gastro-oesophageal reflux disease (GERD)
Södra Hälsocentralen, S-824 81 Hudiksvall and
a Hässle Läkemedel AB, S-431 83 Mölndal, Sweden.
Brun J, Sörngård H and a Swedish multi-centre group in primary health care. High dose proton pump inhibitor response as an initial strategy for a clinical diagnosis of GERD. Family Practice 2000; 17: 401–404.
Received 4 November 1999; Revised 19 April 2000; Accepted 16 May 2000.
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Abstract |
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Background. The diagnosis of gastro-oesophageal reflux disease (GERD) in primary care rests primarily on symptoms. Oesophageal acid exposure is the most important pathogenic factor and it is likely that symptom response to acid inhibition also identifies patients with GERD.
Objective. The aim of this study was to evaluate the outcome of a symptom-based strategy in the management of GERD patients in primary care.
Methods. Patients in general practice with main symptoms of at least moderate heartburn or regurgitation were given omeprazole 20 mg b.i.d. openly for 7 days (first phase). Responders with later relapse were randomized to double-blind treatment with omeprazole 20 mg o.m. or placebo for 2 weeks (second phase). A response in both phases was defined as a decrease by at least three grades on a seven-grade Likert scale and no more than mild intensity of the main symptom.
Results. Of the 362/371 recruited patients who were evaluated in the first phase, 73% were responders. A total of 174/179 patients with a relapse were assessed in the second phase, and 74 and 28% in the omeprazole and placebo group, respectively, were defined as responders (P < 0.001, 95% confidence interval 33–59).
Conclusions. GERD patients are highly responsive to omeprazole 20 mg b.i.d. They are equally responsive to omeprazole 20 mg o.m. at symptomatic relapse, but have a low response rate to placebo. Omeprazole is a valuable therapeutic instrument to detect and treat patients with GERD in general practice.
Keywords. Diagnostic test, gastro-oesophageal reflux disease, omeprazole, primary care.
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Introduction |
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Gastro-oesophageal reflux disease (GERD) is a common dyspeptic disorder affecting almost 40% of the population in the Western world. Heartburn alone or together with regurgitation are the most common symptoms and are sometimes considered diagnostic for patients with GERD. There is poor correlation between reflux symptoms and endoscopic or other objective findings. Only ~30% of the patients with symptoms of GERD have macroscopic findings of oesophagitis at endoscopy1 and, among patients with endoscopically diagnosed oesophagitis, up to 25% will have a normal reflux pattern.
The aim of this study was to describe the outcome of a symptom-based primary care management strategy in GERD patients and to assess the usefulness of omeprazole as a diagnostic tool.
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Methods |
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Patients in general practice between 18 and 70 years old were eligible if their predominant symptom of dyspepsia was either heartburn and/or regurgitation with symptoms for at least 3 days during the past week, a history of GERD symptoms and symptoms of at least moderate intensity at the start of the study. Patients were excluded if they were 45 years or older when the GERD symptoms first appeared, if they presented any alarm symptoms, had a history of peptic ulcer disease or oesophagogastric surgery, if they had used antisecretory drugs within 2 weeks or non-steroidal anti-inflammatory drugs (NSAIDs) within 30 days or had an expected need for NSAIDs during the study. Before enrolment, the patients completed the Psychological Well-Being (PGWB) questionnaire.
The first phase of the study was an open 1 week treatment period with double-dose omeprazole, 20 mg b.i.d. The second phase was a 2 week double-blind treatment period with omeprazole 20 mg o.m. or placebo.
The intensity of heartburn and regurgitation were recorded before the start of treatment and every evening during the treatment in a diary. A seven-grade Likert scale was used, where: 0 = no symptoms, 1 = minor, 2 = mild, 3 = moderate, 4 = quite severe, 5 = severe and 6 = very severe symptoms.
Response after the first phase was defined as a decrease in the main symptom by at least three grades, from the intake of the first omeprazole capsule to 7 days afterwards, and no more than mild intensity of the main symptom on day 7.
Responders were asked to contact their physician again if heartburn and/or regurgitation of at least moderate intensity recurred. They were then randomized to a double-blind comparison of the efficacy of omeprazole 20 mg o.m. and placebo for 2 weeks. Symptoms were recorded in the same way as during the first phase, and the same definition of response was used.
The sample size was calculated to detect a difference in symptom relief of 30% between the two treatments with a power of 90% using a two-tailed test at 5% significance level.
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Results |
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Three hundred and seventy-one patients entered the first phase and it was possible to evaluate 362 of these. Heartburn was predominant in 81% and regurgitation in 19%. On day 7, 73% were responders according to the study definition. There was no difference in response between patients with predominant symptoms of heartburn (73%) and regurgitation (71%), respectively. The distribution of responders each day during the first phase is shown in Figure 1
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The PGWB questionnaire at baseline showed a mean score of 93.4, SD 19.2, for all patients. Responders to omeprazole had a higher total baseline score of 95.2, SD 18.5, compared with non-responders, with 88.6, SD 20.0.
One hundred and seventy-nine patients had recurrence of GERD symptoms within the study period and were randomized to the second phase. One hundred and seventy-four patients could be evaluated (Table 1). The median number of days until symptomatic relapse was 20 (Q1 = 10, Q3 = 69). The treatment groups in the second phase were well balanced with regard to all demographic characteristics and did not differ from the group without relapse.
A total of 74% in the omeprazole group and 28% in the placebo group were responders; P > 0.001 (ITT). The difference was estimated with a 95% confidence interval (CI) of 33–59%. The distribution of responders each day during the second phase is shown in Figure 2.
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If the definition of response was reduced to "relief of symptoms to mild or less", i.e. a less strict but clinically more frequently used definition, the response rate in the omeprazole group was 86% and in the placebo group 51%; P < 0.001, CI 22–48%.
When patients were asked to evaluate the outcome of treatment in the first phase, 87% stated they were already satisfied on day 3. The corresponding figures after the second phase were 77% in the omeprazole group and 28% in the placebo group.
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Discussion |
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Jonsson et al.2 assessed patients with heartburn and regurgitation and used omeprazole 20 mg b.i.d. or placebo during 7 days as a diagnostic test. Among patients with ‘true' GERD, defined either as positive endoscopy or positive 24 h pH monitoring, or both, omeprazole identified 74%. That is a diagnostic yield similar to that of 24 hour pH monitoring,3 but achieved in a much easier way for the patient and at a lower cost to the health care system. This is also in line with the results from a recently published study by Bate et al.4
We brought this concept into practice in a primary care setting. After 7 days with omeprazole 20 mg b.i.d, 87% of the patients were satisfied with the treatment but only 73% were strictly defined as responders. This indicates that the patients' criteria for symptom relief are less stringent than the requirements for ‘response' in the study.
At baseline, the responders reported a mean PGWB score similar to that of GERD patients in other studies.5 The non-responders scored markedly lower, mainly due to a difference in questions related to anxiety. This indicates that anxiety was an important component of their complaint and, though their GERD symptoms were treated with omeprazole, the anxiety had still not been dealt with. These findings are important to bear in mind in the normal clinical situation before we suggest higher doses or change of therapy.
In conclusion, this study shows that most patients with symptomatic GERD will respond to the acid-suppressive effect of omeprazole, and that the proportion of patients who respond to placebo will depend largely on the definition of response. Omeprazole 20 mg b.i.d. for 7 days can be used in clinical practice to confirm or question the diagnosis of GERD. It can be used in a way similar to the reversibility test with ß-adrenoceptor stimulants in the management of bronchial asthma. None of these strategies are conclusive, but they help to corroborate the diagnosis and at the same time assess treatment possibilities.
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Acknowledgments |
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This study was sponsored by Hässle Läkemedel AB, Sweden.
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References |
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1 Venables TL, Newland RD, Patel AC, Hole J, Wilcock C, Turbitt ML. Omeprazole 10 mg once daily, omeprazole 20 mg once daily, or ranitidine 150 mg twice daily, evaluated as initial therapy for the relief of symptoms of gastrooesophageal reflux disease in general practice. Scand J Gastroenterol 1997; 32: 965–973.[Web of Science][Medline]
2 Johnsson F, Weywadt L, Solhaug J-H, Hernqvist H, Bengtsson L. One-week omeprazole treatment in the diagnosis of gastrooesophageal reflux disease. Scand J Gastroenterol 1998; 33: 15–20.[Medline]
3 Fass R, Fennerty MB, Yalam JM, Camargo L, Garewall H, Grade A. Evaluation of the ‘omeprazole test' in patients with typical symptoms of gastrooesophageal reflux disease (GERD). Gastroenterology 1997; 112: A114.
4 Bate CM, Riley SA, Chapman RWG, Durnin AT, Taylor MD. Evaluation of omeprazole as a cost-effective diagnostic test for gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1999; 13: 59–66.[Medline]
5 Dimenäs E, Carlsson G, Glise H, Israelsson B, Wiklund I. Relevance of norm values as part of the documentation of Quality of Life instruments for use in upper gastrointestinal disease. Scand J Gastroenterol 1996; 31(Suppl 221):8–13.
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