Short-term treatment of gastroesophageal reflux disease
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OBJECTIVE: To investigate the efficacy of acid suppressant drugs in the empirical treatment of gastroesophageal reflux disease (GERD) and in the treatment of endoscopy-negative reflux disease (ENRD).
DESIGN: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched. Bibliographies were reviewed.
SETTING: Studies were eligible that compared the short-term use of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) with each other or with placebo in adults with GERD who were enrolled irrespective of endoscopic findings (empirical cases) or in whom endoscopy showed no signs of esophagitis (endoscopy-negative cases).
MEASUREMENTS: Of 1,408 studies, only 13 could be included for meta-analysis. Data on 3,433 patients empirically treated for GERD and 2,520 patients treated for ENRD were extracted. The primary endpoint was relief of heartburn.
MAIN RESULTS: In the empirical treatment of GERD, the summary relative risk (sRR) for symptom relief from H2RAs versus placebo was 0.77 (95% confidence interval [95% CI], 0.60 to 0.99). RR in the only placebo-controlled PPI trial was 0.35 (95% CI, 0.26 to 0.46). The sRR for standard dose PPIs versus H2RAs was 0.55 (95% CI, 0.44 to 0.68). In treatment of ENRD, both PPis (sRR, 0.64; 95% CI, 0.52 to 0.79) and H2RAs (sRR, 0.78; 95% CI, 0.62 to 0.97) were superior to placebo, and PPis were superior to H2RAs (sRR, 0.81; 95% CI, 0.70 to 0.95).
CONCLUSIONS: Acid suppressant therapy (with a PPI or an H2RA) is more effective than placebo for short-term relief of heartburn in patients with persistent symptoms who are treated empirically for GERD and in those in whom esophagitis was excluded after endoscopy. The benefit of PPIs compared with H2RAs is more pronounced in patients treated empirically.
- DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 1999;94:1434–42. CrossRef
- Corder AP, Jones RH, Sadler GH, Daniels P, Johnson CD. Heartburn, oesophagitis and Barrett’s oesophagus in self-medicating patients in general practice. Br J Clin Pract. 1996;50:245–8.
- Isolauri J, Laippala P. Prevalence of symptoms suggestive of gastro-oesophageal reflux disease in an adult population. Ann Med. 1995;27:67–70.
- Locke GR, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997;112:1448–56. CrossRef
- Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis. 1976;21:953–6. CrossRef
- Thompson WG, Heaton KW. Heartburn and globus in apparently healthy people. Can Med Assoc J. 1982;126:46–8.
- Dimenas 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;221(suppl):8–13.
- Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997;112:1798–810. CrossRef
- Kroes RM, Numans ME, Jones RH, de Wit NJ, Verheij TJM. Gastrooesophageal reflux disease in primary care. Comparison and evaluation of existing national guidelines and development of uniform European guidelines. Eur J Gen Pract. 1999;5:88–97. CrossRef
- Joelsson B, Johnsson F. Heartburn—the acid test. Gut. 1989;30:1523–5.
- Johansson KE, Ask P, Boeryd B, Fransson SG, Tibbling L. Oesophagitis, signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal reflux disease. Scand J Gastroenterol. 1986;21:837–47.
- Johnsson F, Joelsson B, Gudmundsson K, Greiff L. Symptoms and endoscopic findings in the diagnosis of gastroesophageal reflux disease. Scand J Gastroenterol. 1987;22:714–8.
- Robinson M, Earnest D, Rodriguez-Stanley S, et al. Heartburn requiring frequent antacid use may indicate significant illness. Arch Intern Med. 1998;158:2373–6. CrossRef
- Tefera L, Fein M, Ritter MP, et al. Can the combination of symptoms and endoscopy confirm the presence of gastroesophageal reflux disease? Am Surg. 1997;63:933–6.
- Dent J. Gastro-oesophageal reflux disease. Digestion. 1998;59:433–45. CrossRef
- Rodriguez-Stanley S, Robinson M, Earnest DL, Greenwood-Van MB, Miner PB Jr. Esophageal hypersensitivity may be a major cause of heartburn. Am J Gastroenterol. 1999;94:628–31. CrossRef
- Shi G, Bruley des Varannes S, Scarpignato C, Le Rhun M, Galmiche JP. Reflux related symptoms in patients with normal oesophageal exposure to acid. Gut. 1995;37:457–64.
- Laird NM, Mosteller F. Some statistical methods for combining experimental results. Int J Technol Assess Health Care. 2003;24:243–6.
- Lau J, Ioannidis JPA, Schmid CH. Summing up evidence: one answer is not always enough. Lancet. 1998;351:123–7. CrossRef
- Engels EA, Schmid CH, Terrin N, Olkin I, Lau J. Heterogeneity and statistical significance in meta-analysis: an empirical study of 125 meta-analyses. Stat Med. 2000;19:1707–28. CrossRef
- Deeks JJ. Issues in the selection of summary statistics of meta-analyses of clinical trials with binary outcomes. Stat Med. 2002;21:1575–600. CrossRef
- Schindlbeck NE, Klauser AG, Voderholzer WA, Muller-Lissner S. Empiric therapy for gastroesophageal reflux disease. Arch Intern Med. 1995;155:1808–12. CrossRef
- Robinson MG, Orr WC, McCallum R, Nardi R. Do endoscopic findings influence response to H2 antagonist therapy for gastroesophageal reflux disease? Am J Gastroenterol. 1987;82:519–22.
- Powell-Jackson P, Barkley H, Northfield TC. Effect of cimetidine in symptomatic gastro-oesophageal reflux. Lancet. 1978;2:1068–9. CrossRef
- Marrero JM, de Caestecker JS, Maxwell JD. Effect of famotidine on oesophageal sensitivity in gastro-oesopahgeal reflux disease. Gut. 1994;35:447–50.
- Johnsson F, Weywadt L, Solhaug J-H, Hernqvist H, Bengtsson L. One-week omeprazole treatment in the diagnosis of gastro-oesophageal reflux disease. Scand J Gastroenterol. 1998;33:15–20. CrossRef
- Johnsson F, Roth Y, Damgaard Pedersen N-E, Joelsson B. Cimetidine improves GERD symptoms in patients selected by a validated GERD questionnaire. Aliment Pharmacol Ther. 1993;7:81–6. CrossRef
- Jebbink HJA, Smout AJPM, van Berge Henegouwen GP. Ranitidine vooral werkzaam bij functionele dyspepsie met klachten passend bij refluxziekten. Ned Tijdschr Geneeskd. 1993;137:1772–5.
- Greaney MG, Irvin TT. Cimetidine for the treatment of symptomatic gastro-oesophageal reflux. Br J Clin Pract. 1981;35:21–4.
- Bennett JR, Buckton G, Martin HD. Cimetidine in gastro-oesophageal reflux. Digestion. 1983;26:166–72. CrossRef
- Johansson KE, Boeryd B, Johansson K, Tibbling L. Double-blind crossover study of ranitidine and placebo in gastro-oesophageal reflux disease. Scand J Gastroenterol. 1986;21:769–78.
- Richter JE, Campbell DR, Kahrilas PJ, Huang B, Fludas C. Lansoprazole compared with ranitidine for the treatment of nonerosive gastroesophageal reflux disease. Arch Intern Med. 2000;160:1803–9. CrossRef
- Schenk BE, Kuipers EJ, Klinkenberg-Knol EC, et al. Omeprazole as a diagnostic tool in gastroesophageal reflux disease. Am J Gastroenterol. 1997;92:1997–2000 (see comments).
- Behar J, Brand DL, Brown FC, et al. Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double blind controlled trial. Gastroenterology. 1978;74:441–8.
- Bright-Asare P, El-Bassoussi M. Cimetidine, metoclopramide, or placebo in the treatment of symptomatic gastroesophageal reflux. J Clin Gastroenterol. 1980;2:149–56. CrossRef
- Fiasse R, Hanin C, Lepot A, Descamps C, Lamy F, Dive C. Controlled trial of cimetidine in reflux esophagitis. Dig Dis Sci. 1980;25:750–5. CrossRef
- Robinson M, Decktor DL, Stone RC, et al. Famotidine (20 mg) b.i.d. relieves gastrooesophageal reflux symptoms in patients without erosive oesophagitis. Famotidine/GERD Investigation Group. Aliment Pharmacol Ther. 1991;5:631–43. CrossRef
- Sabesin SM, Berlin RG, Humphries TJ, Bradstreet DC, Walton-Bowen KL, Zaidi S. Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group. Arch Intern Med. 1991;151:2394–400. CrossRef
- Sontag S, Robinson M, McCallum RW, Barwick KW, Nardi R. Ranitidine therapy for gastroesophageal reflux disease. Results of a large double-blind trial. Arch Intern Med. 1987;147:1485–91. CrossRef
- Watson RG, Tham TC, Johnston BT, McDougall NI. Double blind cross-over placebo controlled study of omeprazole in the treatment of patients with reflux symptoms and physiological levels of acid reflux—the “sensitive oesophagus. Gut. 1997;40:587–90.
- Armstrong D, Pare P, Pericak D, Pyzyk M, Canadian Pantoprazole GERD Study Group. Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease. Am J Gastroenterol. 2001;96:2849–57.
- Bate CM, Green JR, Axon AT, et al. Omeprazole is more effective than cimetidine for the relief of all grades of gastro-oesophageal reflux disease-associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis. Aliment Pharmacol Ther. 1997;11:755–63. CrossRef
- Venables TL, Newland RD, Patel AC, Hole J, Wilcock C, Turbitt ML. Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice. Scand J Gastroenterol. 1997;32:965–73.
- Rush DR, Stelmach WJ, Young TL, et al. Clinical effectiveness and quality of life with ranitidine vs placebo in gastroesophageal reflux disease patients: a clinical experience network (CEN) study. J Fam Pract. 1995;41:126–36 (see comments).
- Bardhan KD, Muller-Lissner S, Bigard MA, et al. Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. The European Study Group. BMJ. 1999;318:502–7.
- Hallerback B, Glise H, Johansson B, et al. Gastro-oesophageal reflux symptoms—clinical findings and effect of ranitidine treatment. Eur J Surg. 1998;583:6–13. CrossRef
- Carlsson R, Dent J, Watts R, et al. Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group. Eur J Gastroenterol Hepatol. 1998;10:119–24. CrossRef
- Riemann JF, Hobel W. Cimetidine suspension in patients with stage 0 gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 1991;5:191–7. CrossRef
- Lind T, Havelund T, Carlsson R, et al. Heartburn without oesophagitis: efficacy of omeprazole therapy and features determining therapeutic response. Scand J Gastroenterol. 1997;32:974–9. CrossRef
- Havelund T, Lind T, Wiklund I, et al. Quality of life in patients with heartburn but without esophagitis: effects of treatment with omeprazole. Am J Gastroenterol. 1999;94:1782–9. CrossRef
- Hatlebakk JG, Hyggen A, Madsen PH, et al. Heartburn treatment in primary care: randomised, double blind study for 8 weeks. BMJ. 1999;319:550–3.
- Bate CM, Griffin SM, Keeling PW, et al. Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis. Aliment Pharmacol Ther. 1996;10:547–55. CrossRef
- Miner PB Jr, Orr W, Filippone J, Jokubaitis L, Sloan S. Rabeprazole in nonerosive gastroesophageal reflux disease: a randomized placebo-controlled trial. Am J Gastroenterol. 2002;97:1332–9. CrossRef
- Richter JE, Peura D, Benjamin SB, Joelsson B, Whipple J. Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis. Arch Intern Med. 2000;160:1810–6. CrossRef
- Short-term treatment of gastroesophageal reflux disease
Journal of General Internal Medicine
Volume 18, Issue 9 , pp 755-763
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- systematic review
- primary care
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- 1. Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, 3508 AB, Utrecht, The Netherlands
- 2. New England Medical Center, Tufts University, Boston, Mass
- 3. Durham University, Durham, England, United Kingdom