Clinical Question

What is the safest and most effective short-term medical treatment for reflux esophagitis?

Evidence-Based Answer

Proton pump inhibitors (PPIs) are the most effective short-term treatment for reflux esophagitis. Histamine H₂ blockers are also effective compared with placebo, but are inferior to PPIs. There is limited evidence about adverse events with these therapies, but long-term therapy with PPIs has been shown to increase hip fracture risk.

Practice Pointers

The authors of this Cochrane review studied the effectiveness of PPIs, H₂ blockers, prokinetics, and sucralfate (Carafate) in the short-term management (two to 12 weeks of therapy) of endoscopically proven reflux esophagitis. The authors reviewed 134 trials, which included 35,978 patients with gastroesophageal reflux disease, to assess the proportion of patients who had persistent reflux esophagitis symptoms or persistent esophagitis.

Five randomized controlled trials (RCTs) that evaluated the effectiveness of standard-dose PPI therapy in 645 participants at eight weeks showed a statistically significant benefit in which esophagitis persisted in 16.8 percent of those on PPIs compared with 71.7 percent on placebo. In other words, 1.7 patients needed short-term treatment with a PPI to benefit, and three patients needed short-term treatment to experience global symptom relief. Head-to-head comparisons between PPIs showed equal effectiveness at standard doses; the only exception was esomeprazole (Nexium), which showed a small benefit compared with omeprazole (Prilosec) in one trial where esophagitis persisted in 35.2 percent of those taking omeprazole versus 29.6 percent taking esomeprazole. However, the dose of esomeprazole was higher than the dose of omeprazole in this trial.

Ten RCTs that evaluated 1,241 participants at six weeks showed a statistically significant benefit of taking an H₂ blocker (esophagitis persistence 59.0 versus 79.7 percent in H₂ blocker and placebo groups, respectively), with a number needed to treat to benefit (NNTB) of 5. Pooled data from 26 RCTs showed a statistically significant benefit of taking PPI therapy compared with H₂ blocker or H₂ blocker plus prokinetics (esophagitis persistence 31.5 versus 61.5 percent in PPI and in the H₂ blocker or H₂ blocker plus prokinetics group, respectively) with an NNTB of 3. There was no statistically significant benefit of prokinetic therapy compared with placebo, or of administering mucosal-protecting agent therapy compared with antacid or placebo.

There were no statistically significant differences in reported adverse events for PPIs or H₂ blockers compared with placebo. The most commonly reported side effects included diarrhea, constipation, and headache; no studies examined adverse events in prokinetic agents compared with placebo. However, a recent nested case control study of 13,556 patients with hip fractures and 135,386 control-group participants older than 50 years concluded that long-term PPI therapy (up to four years), particularly at high doses, is associated with an increased hip fracture risk; this risk increased with increasing cumulative exposure to PPIs.¹

The American College of Gastroenterology (ACG) recommends PPIs for reflux esophagitis, and, although H₂ blockers are less effective, they may be used for less severe cases.² The ACG recommends maintenance therapy at therapeutic or higher daily dosing and cites that up to 50 percent of patients have chronic symptoms that require maintenance or lifelong therapy; the goal of maintenance is to control patients' bothersome symptoms and prevent complications (e.g., esophageal stricture). In light of recent evidence of increased risk of osteoporotic hip fracture with prolonged PPI therapy, it is reasonable to stop treatment in patients who do not continue to require therapy.