Omeprazole was better than ranitidine for maintaining remission in reflux esophagitis
ACP J Club. 1995 Mar-April;122:38. doi:10.7326/ACPJC-1995-122-2-038
Hallerbäck B, Unge P, Carling L, et al., and the Scandinavian Clinics for United Research Group. Omeprazole or ranitidine in long-term treatment of reflux esophagitis. Gastroenterology. 1994 Nov;107:1305-11.
To evaluate the effectiveness of omeprazole and ranitidine in maintaining remission in patients with reflux esophagitis.
Randomized, double-blind, controlled trial with 12-month follow-up.
22 centers in Scandinavia.
426 patients had erosive or ulcerative esophagitis with endoscopic grading of esophagitis ≥ 2. Exclusion criteria were esophageal strictures needing dilatation, concomitant active gastric or duodenal ulcers, esophageal abnormalities, previous esophagogastric surgery, malignancy, pregnancy or lactation, treatment with other investigational drugs, and drug or alcohol abuse. 392 patients (mean age 54 y, 66% men) entered the maintenance phase of the study. 370 patients (94%) completed the study.
After 8 weeks of healing treatment with omeprazole, 20 mg/d, those patients considered healed (gross endoscopic appearance ≤ grade 1) were allocated to omeprazole, 10 mg/d (n = 133), omeprazole, 20 mg/d (n = 131), or ranitidine, 150 mg twice daily (n = 128). Compliance was assessed by tablet count at each clinic visit.
Main outcome measures
Symptomatic and endoscopically confirmed remission and adverse effects.
The estimated proportions of patients in symptomatic remission at 12 months after maintenance treatment with 20-mg omeprazole, 10-mg omeprazole, and ranitidine were 72%, 62%, and 45%, respectively. Both dosages of omeprazole were superior to ranitidine (20 mg omeprazole compared with ranitidine P < 0.001, 10-mg omeprazole compared with ranitidine P < 0.005) (Table). The estimated proportion of patients in endoscopic remission with 20-mg omeprazole, 10-mg omeprazole, and ranitidine were 77%, 58%, and 46%, respectively. 20-mg omeprazole was superior to both 10-mg omeprazole (P = 0.003) and ranitidine (P < 0.001) (Table). Epigastric pain (5.9%) and diarrhea (5.2%) were the most commonly reported adverse effects; 8 patients (1.9%) discontinued treatment. The groups did not differ for adverse effects.
Omeprazole, 20 or 10 mg/d, was more effective than ranitidine, 150 mg twice daily, in maintaining remission in patients with reflux esophagitis.
Source of funding: In part, Astra Hässle.
For article reprint: Dr. B. Hallerbäck, Department of Surgery, Norra Älvsborgs Länssjukhus, S-461 85 Trollhättan, Sweden. FAX 46-520-91726.
Table. Omeprazole, 10 mg/d or 20 mg/d, vs ranitidine for reflux esophagitis*
|Outcomes at 12 mo||Comparisons||Event rates||RBI (95% CI)||NNT (CI)|
|Symptomatic remission||10-mg omeprazole vs ranitidine||62% vs 45%||36% (8 to 73)||7 (4 to 24)|
|20-mg omeprazole vs ranitidine||72% vs 45%||58% (28 to 99)||4 (3 to 7)|
|Endoscopic remission||10-mg omeprazole vs ranitidine||58% vs 46%||26% (-1 to 60)||Not significant|
|20-mg omeprazole vs ranitidine||77% vs 46%||67% (37 to 108)||3 (2 to 5)|
|20-mg omeprazole vs 10-mg omeprazole||77% vs 58%||33% (13 to 59)||6 (4 to 13)|
*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.
This excellent study confirms the previous finding (1) that the proton pump inhibitor omeprazole is superior to histamine-2 (H2)-blockers in keeping reflux symptoms and esophagitis in remission for 1 year. Although higher, more frequent doses of H2-blockers may yield similar efficacy, they would prove more expensive and less convenient than the proton pump inhibitors, and would be plagued by the same safety issues.
In December 1994, the U.S. Food and Drug Administration (FDA) Advisory Board recommended approval of ranitidine and proton pump inhibitors for all forms of chronic reflux disease, whereas omeprazole and the newest proton pump inhibitor, lansoprazole, received approval for patients with severe persistent symptoms and esophagitis.
Despite FDA support, caution in patient selection and choice of therapy is warranted. Most patients with reflux symptoms without esophagitis will not need long-term continuous therapy. They can be treated with lifestyle changes and short-term medications. Therefore, the main criteria for maintenance therapy will be symptom relapse and the presence of esophagitis. Baseline endoscopy with symptom recurrence accurately assesses the presence and severity of esophagitis. Patients with mild esophagitis may be treated with maintenance H2-blockers. Patients with more extensive erosions, ulcerations, or stricture will need maintenance therapy with omeprazole or lansoprazole at the lowest dose to eliminate symptoms.
Long-term safety and efficacy remain unresolved. H2-blockers, however, have been used for up to 15 years and have an excellent safety profile. A recent cohort study with omeprazole found sustained healing of severe esophagitis for up to 5 years, although some patients required doses as high as 60 mg/d (2). Safety with the proton pump inhibitors is problematic and has an evolving story. Enterochromaffin-like cell hyperplasia has been reported after prolonged use, but carcinoid tumors have not occurred in uncomplicated reflux or ulcers. Nevertheless, healthy and, particularly, young patients need to be advised of potential safety issues and should be counseled about antireflux surgery done by a skilled and experienced surgeon.
Joel E. Richter, MD
The Cleveland Clinic FoundationCleveland, Ohio, USA