The available evidence summarized in this meta-analysis suggests that a short course with any of the antisecretory drug classes investigated is effective in controlling symptoms in patients with GERD treated empirically, and in patients who have symptoms of GERD but no abnormal findings on endoscopy. Only 1 placebo-controlled PPI trial51
on short-term empirical treatment for GERD was identified, probably reflecting the ethical considerations of using placebo in symptomatic patients. In empirical treatment of GERD, PPIs (standard or half dose) were superior to H2
RAs (standard dose) in all trials in which they were compared. In ENRD, standard dose PPIs were more effective than H2
RAs; there were insufficient data to make any conclusions regarding low dose PPIs in patients with ENRD.
The use of antacids as rescue medication was allowed in most of the trials in this study. In general, patients randomized to less-effective therapy used more antacids. It is possible that this trend reduced the estimate of the treatment benefit in patients receiving the more-effective therapy. Interestingly, it also may contribute to the high healing rates that have been observed in placebo groups in clinical trials of patients with esophagitis.8
It can be argued that our empirical group was not truly empirical, since endoscopy was performed in all but 1 trial and some patients were excluded because of either severe or complicated esophagitis or peptic ulcer disease. Most of the studies did not report the number of patients excluded based upon endoscopic findings. In 1 of the studies that did,46
only 14 out of 441 patients (3%) were excluded on the basis of these endoscopic findings. Thus, we believe that the empirical group represented a good reflection of the adult population presenting with a history of serious and relatively long-standing but uncomplicated GERD.
Only studies with binary data on complete or near-complete symptom relief, a relatively strict definition of treatment success, were included in our formal meta-analysis. Although this reduced the number of eligible studies, it also selected for studies that used relatively uniform outcome definitions, making it easier to translate the results to daily practice. However, a more standardized outcome measure for assessment of symptom relief would be desirable for future studies. Similarly, only a few studies reported changes in validated quality-of-life instruments, and the majority of the quality-of-life instruments used in these studies were not specifically designed for patients with GERD. This important component of clinical efficacy should be incorporated more consistently into future trials.
The chronic relapsing nature of GERD usually requires long-term maintenance treatment. Our study focused only on short-term treatment trials, and thus results cannot be extrapolated into maintenance therapy. Relatively few studies were available for analysis considering that the population that we focused on represents the majority of patients seeking care for symptoms of GERD. More studies are needed comparing different classes of medications.
In conclusion, the available evidence suggests that short-term treatment with antisecretory drugs is effective for patients with typical symptoms of GERD who are treated empirically and for those with typical symptoms who did not have endoscopic signs of esophagitis. Superiority of PPIs (standard dose) to H2RAs was demonstrated in patients treated empirically (RR, 0.55; 95% CI, 0.44 to 0.68), as well as in the treatment of those without esophagitis on endoscopy (ENRD; RR, 0.81; 95% CI, 0.70 to 0.95). Standard dose PPIs were slightly less superior to H2RAs in the ENRD compared with the empirical group. One possible explanation may be that the empirical group had a higher proportion of patients with esophagitis; such patients generally respond better to PPIs than to H2RAs. Thus, the choice of drug classes in early empirical treatment of GERD might ideally depend on an estimate of the likelihood of esophagitis, since in those without esophagitis, PPI therapy may not always be necessary. To improve the possibilities of translating these results into strategies for pragmatic care, more needs to be learned about identifying patients with “typical” GERD symptoms and about estimating the proportion of those with mucosal damage due to GERD. In addition, most of the patients in this meta-analysis had symptoms for only a moderate length of time, while “true” GERD is considered to be a chronic disease. Thus, the conclusion that standard dose PPI therapy is superior to H2RAs for the initial short-term treatment of GERD can only be drawn for primary care patients or outpatients in general internal clinics presenting with relatively serious and/or recurring heartburn. Patients with less-typical symptoms or only having symptoms for a short time might benefit equally from H2RA or PPI therapy.