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


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


METHODS
Patients receiving ambulatory care from referral centers.


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


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


METHODS
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.
Klinkenberg-Knol
E C
EC
Free University Hospital, Department of Gastroenterology, Amsterdam, the Netherlands.
Festen
H P
HP
Jansen
J B
JB
Lamers
C B
CB
Nelis
F
F
Snel
P
P
Lückers
A
A
Dekkers
C P
CP
Havu
N
N
Meuwissen
S G
SG
D001471:Barrett Esophagus / Q000188:drug therapy; D004351:Drug Resistance; D004942:Esophagitis, Peptic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005755:Gastrins / Q000097:blood; D005773:Gastroscopy; D006801:Humans; D015993:Life Tables; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D005755:Gastrins; D009853:Omeprazole