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Previous Volume 338:727-734 March 12, 1998 Number 11 Next

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ABSTRACT

Background Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs.

Methods In a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 µg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 µg of misoprostol twice daily, or placebo for six months.

Results At eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P = 0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively).

Conclusions The overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol.

Source Information

From the Division of Gastroenterology, University Hospital, Nottingham, United Kingdom (C.J.H.); the Peninsula Specialist Centre, Kippa Ring, Australia (J.A.K.); the Department of Rheumatology, University Medical School, Lublin, Poland (L.S.); Sunshine Coast Day Surgery, Maroochydore, Australia (D.G.W.); the Division of Gastroenterology, Montreal General Hospital, Montreal (A.B.); the Rheumatology Unit, City Hospital, Nottingham, United Kingdom (A.J.S.); and the Department of Medicine, University of Melbourne, Western Hospital, Melbourne, Australia (N.D.Y.). This article is dedicated to the memory of Mr. Eugen Taure, who died on July 9, 1996.

Address reprint requests to Dr. Hawkey at the Nottingham Gastrointestinal Trials Service, Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, United Kingdom.

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