A placebo-controlled investigation of duodenal ulcer recurrence after withdrawal of long-term treatment with ranitidine.

Ninety-two patients with duodenal ulcer disease, who had received long-term continuous treatment with ranitidine for an average of 7.5 years, participated in a double-blind, placebo-controlled study to determine whether stopping ranitidine resulted in ulcer recurrence. Patients were randomized to continue with ranitidine (n = 46) or to receive placebo (n = 46) and were followed up for six months. Treatment failure was defined as the first symptomatic recurrence of ulcer. The occurrence of epigastric pain during the follow-up period was significantly less frequent in the ranitidine group (13%) than in the placebo group (43%) (P = 0.001). At six months, 9% of the ranitidine group had developed ulcer recurrence, compared with 48% in the placebo group (P < 0.001, logrank test). Multivariate analysis using the Cox proportional hazards model showed that younger age (P = 0.041) and a long history of ulcer disease (P = 0.025) were risk factors for ulcer recurrence but gender, smoking and duration or dose of previous ranitidine treatment were not predictive of relapse during treatment with placebo. In conclusion, withdrawal of ranitidine after more than five years of continuous treatment results in almost half of the patients developing symptomatic ulcer recurrence within six months. Thus, long-term continuous therapy does not alter the natural history of duodenal ulcer disease. Younger patients and those with a long history of ulcer disease appear to be at increased risk of developing ulcer recurrence if long-term treatment is withdrawn.