Ranitidine in the prevention of non-steroidal anti-inflammatory drug-associated gastric and duodenal ulceration in arthritic patients

Abstract

Objective: To perform a meta-analysis of six similarly designed placebo-controlled studies to evaluate the use of ranitidine as prophylaxis for non-steroidal anti-inflammatory drug (NSAID)-associated gastric and duodenal ulceration. Design: All prospective multicentre, double-blind, randomized, placebo-controlled studies of at least 4 weeks duration assessing the prophylactic use of ranitidine 150 mg twice daily in adult arthritic patients taking NSAIDs were included in the meta-analysis. Setting: Twelve hundred out-patients attending 101 centres, including both public and private mainly hospital-based clinics in nineteen countries, entered the studies. Patients: A total of 1200 arthritic patients requiring NSAID therapy who had no or minor (assessed on a modified Lanza scale) gastric or duodenal mucosal damage at baseline endoscopy were included. Overall, 1054 (88%) patients underwent endoscopy after 4 weeks of study treatment. Interventions: Patients were randomized to receive ranitidine 150 mg twice daily (n = 597) or placebo (n = 603) and prescribed an NSAID as specified in the study protocols. Endoscopy was performed immediately prior to treatment and after 4 weeks of study medication. Main outcome measure: The evaluation of primary efficacy was based on endoscopic assessment of patients at 4 weeks. Treatment failure was defined as development of a gastric or duodenal ulcer (≥0.5 cm in diameter with perceptible depth). Ulcer occurrence rates were compared between the two treatment groups using an extended Mantel-Haenszel Chi-squared test. Results: By 4 weeks, ulceration had occurred in 19 (3.2%) of the 597 patients treated with ranitidine 150 mg twice daily compared with 47 (7.8%) of the 603 patients taking placebo (P< 0.005). Duodenal ulcers developed in five patients receiving ranitidine compared with 24 receiving placebo (P<0.005) and gastric ulcers developed in 14 patients receiving ranitidine compared with 24 receiving placebo (P=0.08). Logistic regression confirmed the above treatment effect after adjusting for risk factors, and also revealed the significant effect of a history of peptic ulcer disease on ulcer development (odds ratio, 0.30; 95% confidence interval, 0.16–0.59, P<0.001). The findings were consistent across the six studies. Conclusion: Ranitidine significantly reduces the frequency of duodenal ulceration, but not gastric ulceration, in arthritic patients during 4 weeks of NSAID therapy.