Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety

Ann Intern Med. 1994 Aug 1;121(3):161-7. doi: 10.7326/0003-4819-121-3-199408010-00001.


Objective: To evaluate the long-term efficacy and safety of omeprazole in patients with gastroesophageal reflux disease resistant to treatment with histamine-2 (H2)-receptor antagonists.

Design: Cohort analytic study with a mean follow-up of 48 months (range, 36 to 64 months).

Setting: Patients receiving ambulatory care from referral centers.

Patients: 91 patients with gastroesophageal reflux disease resistant to treatment with an H2-receptor antagonist but subsequently responsive to 40 mg of omeprazole daily.

Intervention: Open maintenance therapy consisting of 20 mg of omeprazole daily in 86 patients and 40 mg daily in 5 patients.

Outcome measures: Endoscopy to assess healing; side effects, laboratory values, fasting serum gastrin level, and gastric corpus biopsies to assess safety.

Results: Esophagitis recurred in 47% of the patients receiving 20 mg of omeprazole daily, but all rehealed after the dose was doubled. Seven of 40 patients (18%) had a second relapse after a mean follow-up time of 24 months (range, 9 to 36 months) that was successfully treated with a further 20-mg dose increment for a mean period of 36 months (range, 6 to 39 months). Median gastrin levels increased initially from 60 ng/L before study entry to 162 ng/L (P < 0.01) with treatment and reached a plateau during maintenance treatment. Very high gastrin levels (> 500 ng/L) were observed in a subgroup (11%) of patients. The incidence of micronodular hyperplasia increased from 2.5% of the patients at first biopsy to 20% at the last biopsy (P = 0.001), with a corresponding progression of gastritis to subatrophic or atrophic gastritis from less than 1% to 25% (P < 0.001), which was more pronounced in patients with very high serum gastrin levels.

Conclusions: Maintenance therapy with omeprazole was effective for at least 5 years in patients with gastroesophageal reflux disease resistant to treatment with H2-receptor antagonists. Treatment was accompanied by a persistent increase in serum gastrin levels and an increase of micronodular argyrophil cell hyperplasia and subatrophic or atrophic gastritis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Barrett Esophagus / drug therapy
  • Drug Resistance
  • Esophagitis, Peptic / blood
  • Esophagitis, Peptic / drug therapy*
  • Esophagitis, Peptic / pathology
  • Female
  • Gastrins / blood
  • Gastroscopy
  • Humans
  • Life Tables
  • Male
  • Omeprazole / administration & dosage
  • Omeprazole / adverse effects
  • Omeprazole / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Gastrins
  • Omeprazole