Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease

Heartburn affects 25% of the adult population on a monthly basis and represents the core symptom of gastro-oesophageal reflux disease (GORD). Treatment is readily available and puts a large demand on healthcare budgets. A majority of GORD patients show no endoscopic abnormalities and in daily practice most patients are treated empirically. Summarise, quantify and compare the efficacy of the short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in adults with GORD and endoscopy negative reflux disease (ENRD). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to December 2003), EMBASE (January 1988 to December 2003). Randomised controlled trials focussing on symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be classifiable in the empirical treatment group (no endoscopy used in treatment allocation) or in the endoscopy negative reflux disease group (no endoscopic signs of erosive oesophagitis). Two reviewers independently assessed trial quality and extracted data. Twenty-seven trials (8402 participants) were included: thirteen in the empirical treatment group, ten in the ENRD group and four in both. In empirical treatment of GORD the relative risk (RR) for heartburn remission in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were significantly (p < 0.05) more effective than H2RAs (five trials, RR 0.69, 95% CI 0.61 to 0.77) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, RR for heartburn remission for PPI versus placebo was 0.68 (six trials, 95% CI 0.59 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.74 (three trials, 95% CI 0.53 to 1.03) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). The findings in this review suggest that antisecretory drugs are effective in the empirical treatment of complaints likely to originate from GORD and in treatment of ENRD and furthermore that PPIs are superior to H2RAs in empirical treatment of typical GORD symptoms.