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.