Should GERD Therapy Be Stepped Up, Stepped Down, or Not Stepped at All?

Kenneth R. DeVault, MD, FACG


May 16, 2003

In This Article

Acid Suppression for GERD

Gastroesophageal reflux disease (GERD) is a chronic condition that produces both symptoms and mucosal damage. The underlying pathophysiology of the condition involves the inappropriate movement of acid from the stomach into the esophagus. Although hypersecretion of acid is very unusual in GERD, treatment centers on the suppression of acid. In fact, acid suppression is the mainstay of therapy for GERD. Proton-pump inhibitors (PPIs) provide the most rapid symptomatic relief and heal esophagitis in the highest percentage of patients. Although less effective than PPIs, histamine-2-receptor blockers given in divided doses may also be used in patients with less severe GERD.

When the results of 33 randomized trials with over 3000 patients were reviewed, symptomatic relief was seen in 27% of placebo-treated, 60% of histamine-2 receptor antagonist (H2RA)-treated, and 83% of PPI-treated patients.[1] Esophagitis healed in 24% of placebo-treated, 50% of H2RA-treated, and 78% of PPI-treated patients. It is clear that while some patients will have relief of symptoms and improvement or healing of esophagitis on H2RAs, PPIs eliminate symptoms and heal esophagitis more frequently and more rapidly than the other agents. Both higher and more frequent doses of H2RAs appear to be more effective in the treatment of reflux symptoms and in healing of esophagitis, but are still inferior to PPIs and are more costly at these higher dosages.[2,3,4] In addition to controlling symptoms and esophagitis, omeprazole therapy has been shown to normalize the impaired quality of life caused by GERD.[5] PPIs are safe, effective, and have been used for more than a decade in the United States and much longer in Europe and Australia.[6] It is becoming increasingly clear that the benefit of chronic PPI therapy in patients with chronic and/or complicated GERD outweighs any theoretical risk.

There are 5 available PPIs: omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. All of these agents have been demonstrated to control GERD symptoms and to heal esophagitis. Several physiologic studies have suggested small benefits of one agent over another, but comparisons between the efficacy of the agents are limited when clinical end points are used. A large study randomized patients with esophagitis to receive either omeprazole 20 mg or lansoprazole 30 mg daily. There were no significant differences between the outcomes of the 2 groups, with identical healing at 8 weeks.[7] Similarly, approximately 200 patients with esophagitis were randomized to either omeprazole 20 mg or rabeprazole 20 mg and had identical healing at both 4 and 8 weeks.[8] Finally, another trial of approximately 200 patients with esophagitis found no difference between omeprazole 20 mg daily and pantoprazole 40 mg daily.[9] Esomeprazole (the s-isomer of omeprazole) has been purified and found to have superior activity to racemic omeprazole in physiologic and gastric pH studies. In a large trial, esomeprazole 40 mg was found to be clinically superior (symptoms and esophagitis) to omeprazole 20 mg, with an 8-week healing rate of 94% for esomeprazole and 87% for omeprazole (P < .05).[10] This difference was particularly impressive in patients with more severe grades of esophagitis. Esomeprazole 40 mg has also been found to be superior to lansoprazole 30 mg in the healing of esophagitis.[11]

The effect of PPIs can be optimized with appropriate dosing. The drugs should always be given before meals. Most patients on once-daily PPIs should take them before breakfast, but a recent study suggested that nighttime acid might be better controlled if the PPI is taken before the evening meal.[12] When a second dose is added, it should be given before the evening meal, not at bedtime. The benefit of complete acid control in the maintenance of Barrett's esophagus has not been proven, but if this result is desired, many patients will need twice-daily PPI therapy at higher-than-usual doses even when they are asymptomatic on lower doses.[13,14] Gastric acid is still secreted, particularly at night, in many patients on twice-daily PPIs.[15] The addition of nighttime H2RA was suggested to suppress this acid, although results of a recent study suggest that this effect is short-lived and may not be clinically significant.[16]