Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Famotidine reduced heartburn and increased healing in gastroesophageal reflux disease

ACP J Club. 1992 May-June;116:73. doi:10.7326/ACPJC-1992-116-3-073


Source Citation

Sabesin SM, Berlin RG, Humphries TJ, et al. Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. Arch Intern Med. 1991 Dec;151:2394-400.


Abstract

Objective

To evaluate the efficacy of oral famotidine, 40 mg, taken at bedtime or 20 mg, twice daily, for the symptomatic relief of gastroesophageal reflux disease and the healing of esophageal erosions or ulcerations.

Design

Randomized, double-blind, placebo-controlled trial of 2 famotidine regimens, of 12 weeks duration.

Setting

18 centers in the United States.

Patients

Patients aged ≥ 18 years with a diagnosis of gastroesophageal reflux disease (heartburn occurring on ≥ 15 of the 30 days before enrollment, with erosive esophagitis confirmed by endoscopy or, if no erosions, by a positive Bernstein acid infusion test) were included. Patients without erosive esophagitis had to have ≥ 5 days of heartburn during a baseline week of medication with placebo. Persons with additional gastrointestinal or other unstabilized disorders, those taking other medications, and pregnant or lactating women were excluded. 64 of 338 patients (19%) enrolled were lost to follow-up.

Intervention

135 patients were randomized to receive oral famotidine, 40 mg, at bedtime; 137, to famotidine, 20 mg, twice daily; and 66, to placebo.

Main outcome measures

Daytime and night-time heartburn (scale, 0 to 4) was recorded in patients' diaries. Therapeutic success was defined as no heartburn for ≥ 5 of 7 days during weeks 2, 6, and 12, and the occurrence of mild heartburn only. Healing of erosive esophagitis required no abnormalities beyond mild erythema or hyperemia.

Main results

At 12 weeks, 75%, 66%, and 47% of patients on the twice-daily regimen, once-daily regimen, and placebo, respectively, were therapeutic successes (P ≤ 0.05 for the differences between the famotidine regimens and placebo). After adjustment for baseline severity, the twice-daily regimen was superior to the once-daily regimen in giving complete daytime relief from heartburn (56% vs 42%, P < 0.05). {This absolute risk reduction of 14% means that 7 patients would need to be treated with twice-daily famotidine, (rather than once daily) to prevent 1 additional patient from having heartburn, 95% CI 4 to 48; the relative risk reduction was 25%, CI 4% to 42%.}* Both the twice-daily and the once-daily famotidine regimens increased the proportion of patients with endoscopic healing (55% and 50%, respectively, vs 37% for placebo, P < 0.05). The groups did not differ in adverse events.

Conclusions

Famotidine was effective in reducing heartburn and promoting healing of erosions in patients with gastroesophageal reflux disease. Two 20-mg doses per day were more beneficial than a single 40-mg bedtime dose.

Source of funding: Merck Sharp & Dohme Research Laboratories.

Address for article reprint: Dr. S.M. Sabesin, Section of Digestive Diseases, Rush-Presbyterian-St. Luke's Medical Center, 1725 West Harrison, Suite 206, Chicago, IL 60612, USA.

*Numbers calculated from data in article.


Commentary

Gastroesophageal reflux disease is different from peptic ulcer disease. Despite this simple admonition, many physicians still treat reflux disease like ulcer disease with their primary goal being suppression of nocturnal acid secretion. Daytime acid reflux is, however, the major factor in these patients' report of symptoms and a contributing factor to the perpetuation of their esophagitis (1). Furthermore, acid reflux is greatest during the day, particularly after the evening meal, and less while patients are asleep (2). The study by Sabesin and colleagues confirms these physiologic observations.

Does this mean that all patients with gastroesophageal reflux disease need to be immediately started on twice-daily doses of an H2 blocker? No, treatment should be individualized to the severity of the patient's symptoms and degree of esophagitis (3). Mild and infrequent symptoms may be treated effectively with simple lifestyle changes and, if needed, antacids or alginic acid. Frequent heartburn, mild esophagitis, or both can be treated with promotility drugs or H2 blockers. A regimen of twice daily H2 blockers for at least 8 to 16 weeks is safer and more effective than promotility drugs. All the H2 blockers are equally effective if used twice daily in proper doses (cimetidine, 800 mg; ranitidine, 150 mg; famotidine, 20 mg; or nizatidine, 150 mg). If symptoms and esophagitis abate, the dose can be reduced to a once-daily dose given at the time symptoms are most prevalent. Patients with severe symptoms, especially associated with erosive and ulcerative esophagitis, are best treated acutely with omeprazole. H2-blocker therapy at increased or more frequent doses is not a good alternative because these regimens are less effective and more expensive and impractical.

Joel E. Richter, MD
University of AlabamaBirmingham, Alabama, USA

Joel E. Richter, MD
University of Alabama
Birmingham, Alabama, USA


References

1. DeCaestecker JS, Blackwell JN, Pryde A, Heading RC. Gut. 1987;28:519-25.

2. Gudmundssen K, Johnsson F, Joelsson B. Scand J Gastroenterol. 1988;23:75-9.

3. Fennerty MB, Sampliner RE. Arch Intern Med. 1991;151:2365-6.