Risk Factors For Duodenal Ulcer Recurrence: Three-year Follow-up during Famotidine Maintenance Therapy

The recurrence-free rate and factors related to recurrence after healing were investigated in duodenal ulcer patients on H₂-blocker maintenance therapy with famotidine. Famotidine maintenance therapy (20 or 40 mg once a day before bedtime) was performed in 488 evaluable patients after endoscopically-proven healing of ulcers (S₁ or S₂). The cumulative recurrence-free rates were 81.1%, 65.1% and 58.2%, respectively, after one, two and three years of maintenance therapy. Among various background factors, those which have been suggested to be closely associated with ulcer recurrence were compared on the basis of their relation to the recurrence-free rate. These factors included a past history of duodenal ulcer, smoking, alcohol use, bulbar deformation, the endoscopic stage of ulcer healing, concomitant drugs and compliance with famotidine therapy. Recurrence correlated most significantly with a past history of duodenal ulcer and with compliance. Compliance was categorized as excellent, good, fair or poor. The recurrence-free rate was significantly lower in patients with excellent compliance than in any other compliance group. A famotidine dose of 40 mg/day (the standard dose), versus the half dose of 20 mg/day, produced no significant difference in the cumulative recurrence-free rate and it was therefore suggested that 20 mg/day of famotidine is comparable to 40 mg/day in its preventive effect on duodenal ulcer recurrence. In addition, because recurrence was more common in patients who had previously experienced recurrence, a past history of ulcer was suggested to be a significant risk factor for ulcer recurrence.     

Ulcer recurrence among Filipino patients: Clinical profile and risk factors

Abstract Patients with endoscopic diagnosis of gastric and/or duodenal ulcers who eventually had endoscopic confirmation of ulcer healing after any anti-ulcer medication were entered in a 3 year study to determine ulcer recurrence rate, onset of ulcer recurrence and factors associated with ulcer recurrence. Patients from two participating centres who are not on any maintenance treatment had endoscopic examinations at 3, 6 and 12 months after ulcer healing or at any time of symptom recurrence. There were 144 patients entered into the study. The 1 year recurrence rate observed among 125 Filipino patients who completed the study was 73% wherein 71% occurred within the first six months. This was comparable with those reported in the world literature. Thirty-three per cent of those with recurrent ulcers were asymptomatic. The difference in the recurrence rate between gastric and duodenal ulcers was not statistically significant. The only risk factors found to be associated with ulcer relapse were history of smoking and alcohol intake. CLO test for Helicobacter pylori done in 45 patients with recurrent ulcers were all positive, suggesting a strong association between H. pylori and ulcer recurrence.     

Incompletely and completely healed duodenal ulcers' outcome in maintenance treatment: a double blind controlled study.

A six month, double blind, controlled study was performed in 107 asymptomatic duodenal ulcer patients who, after short term cimetidine treatment, showed complete or incomplete endoscopic healing. Patients were stratified according to the type of healing and randomly allocated to cimetidine (200 mg at lunch, 400 mg at bedtime) or placebo. Endoscopic examinations were carried out after six months or when symptoms recurred. Eighty seven patients completed the maintenance trial. Of the 56 patients admitted to the study with complete healing, 30 were placed on cimetidine and 26 on placebo. Of the 31 patients admitted with incomplete healing, 15 were placed on cimetidine, and 16 on placebo. Results showed that, regardless of maintenance treatment, patients with incompletely healed ulcers had a higher ulcer crater recurrence rate, than patients with complete healing (71% vs 34%; p less than 0.005). A significantly higher ulcer crater recurrence was observed in incompletely healed ulcer patients, even when cimetidine or placebo treatment groups were considered separately. Irrespective of the type of healing, ulcer crater recurrence was more frequent in placebo treated patients than in those treated with cimetidine (67% vs 29%; p less than 0.001). We conclude that, in order to prevent a high ulcer recurrence rate, maintenance treatment should start only after the assessment of a complete endoscopic healing of duodenal ulcers.     

Recurrent ulcer after successful treatment with cimetidine or antacid

This study was designed to compare the rates of duodenal ulcer healing and recurrence after treatment with cimetidine or antacid. Patients with endoscopically documented duodenal ulcer received cimetidine, 1200 mg daily, or Mylanta II, 7 oz daily, in a randomized, double-blind trial. For the 69 patients in each group who completed the healing phase of the trial, endoscopic ulcer healing was almost identical. At 2, 4, and 6 wk, the cumulative percent healed on antacid was 33%, 64%, and 80%, and on cimetidine it was 25%, 62%, and 86%. The 114 patients with healed ulcer were observed on no therapy and underwent additional endoscopy to detect recurrences when symptomatic or at 3, 6, and 12 mo. There was no difference in the frequency of recurrences between treatments. At 3 and 6 mo, the cumulative percentages of patients with recurrence were 29% and 56% after antacid therapy and 36% and 55% after cimetidine therapy. Some patient variables were associated with delayed ulcer healing or ulcer recurrence. These included sex, pain frequency, smoking, disease duration, and acid secretion.     

Effects of treatment compliance and overnight gastric secretion on outcome of maintenance therapy of duodenal ulcer with ranitidine

Eighty-seven patients with endoscopically healed duodenal ulcers received continuous maintenance treatment with a standard dose of 150 mg ranitidine at night for 6-12 months. The cumulative annual rate of symptomatic reulceration was 24%, whereas a further 25% of asymptomatic relapses were detected with routine endoscopic examination. Compliance with drug therapy was assessed by urinalysis for ranitidine and by returned tablet count. Urinalysis appeared to provide the more accurate index of drug intake. Compliance was similar in patients whose ulcers remained healed after 1 year's treatment and in patients with asymptomatic recurrence. Patients who developed symptomatic recurrences showed significantly poorer compliance in the period before development of symptoms. Overnight secretion of acid and pepsin during treatment did not differ between patients whose ulcers remained healed and those with relapses. Poor compliance was not implicated in the development of recurrence in patients who had good inhibition of overnight gastric secretion. We conclude that duodenal ulceration can recur during nocturnal maintenance treatment despite good compliance and satisfactory inhibition of nocturnal gastric secretion. However, symptomatic manifestation of the recurrences reflects poor compliance with treatment.     

Flow cytometric analysis of cell proliferation kinetics during duodenal ulcer healing

Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12 normal subjects were investigated. Biopsy samples were obtained during endoscopic examination and subjected to DNA analysis by flow cytometry. Thirty patients with duodenal ulcers were healed within 3 months with H₂ blockers (tractable or responsive ulcers), whereas 10 patients did not respond to treatment (intractable ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell proliferation, was constant in the adjacent duodenal mucosa 2cm from ulcer margin and antral mucosa during duodenal ulcer healing. The index at the margin of tractable ulcers was elevated during the active stage (12.9 ± 1.3), peaked during the healing stage (15.4 ± 2.8) and returned to the same level at the scarring stage (10.9 ± 2.0) as normal controls (10.3 ± 1.7). However, the index was not elevated in intractable ulcers (10.3 ± 1.7 in the healing stage) and was smaller than in tractable ulcers. These data indicate that augmented mucosal cell proliferation at the ulcer margin plays an important role in duodenal ulcer healing and intractable ulcers are characterized by an abnormal failure to accelerate DNA synthesis to achieve ulcer repair.     

Prevention of duodenal ulcer recurrence by pirenzepine 50 mg twice daily

Eighty-four patients with healed duodenal ulcers were treated for 1 year with pirenzepine, 50 mg twice daily, or placebo in this double-blind, randomized, multicenter trial. Clinical follow-up and endoscopy were performed before and after 3, 6, and 12 months of treatment. Endoscopy was also carried out whenever symptoms compatible with ulcer recurrence were present for more than 2 days. Both groups were well matched for age, sex, duration of peptic ulcer disease, and smoking habits. There were 21 drop-outs due to lack of compliance. Therefore, 32 patients treated with pirenzepine and 31 with placebo were included in the analysis. Expressed in cumulative percentage of recurrence, with pirenzepine, 28% of the patients had a relapse at 3 months, 41% at 6 months, and 53% at 12 months; with placebo, the recurrence rates were 58% at 3 months, 68% at 6 months, and 71% at 12 months. The mean success time at 1 year is also longer for pirenzepine (7.38 months) than for placebo (5.52 months). These differences are significantly in favor of pirenzepine (p less than 0.05). Both treatments were well tolerated. Dry mouth was more frequently observed with pirenzepine (14 versus 5 patients). We conclude that pirenzepine, 50 mg twice daily, significantly reduces the relapse rate of duodenal ulcers during a 1-year maintenance treatment.     

Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study

OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) in patients with uncomplicated duodenal ulcers prevents long-term recurrence of ulcers. We aimed to study whether treatment of H. pylori prevents the long-term recurrence of duodenal ulcer hemorrhage. METHODS: Patients with duodenal ulcer bleeding and confirmed H. pylori infection were recruited. A total of 120 patients were randomly assigned to triple therapy (DeNoltab 120 mg, amoxycillin 500 mg, and metronidazole 300 mg four times daily) or DeNoltab 120 mg four times daily alone. No maintenance therapy was given during the follow-up period. The endpoints were the cumulative rates of symptomatic and bleeding duodenal ulcer recurrences. RESULTS: Of the patients receiving the triple regimen, 85.1% had H. pylori eradicated as compared to 2.0% of patients receiving DeNoltab (p < 0.05). More patients in the DeNoltab group than those in the Triple group had recurrence of ulcer bleeding, but this did not reach statistical significance (12/60 vs 6/60, p = 0.20). Logistic regression analysis on clinical, personal, and endoscopic characteristics identified persistent H. pylori infection as the only independent predictor of recurrence of duodenal ulcer bleeding. CONCLUSIONS: Treatment of H. pylori alone with the present bismuth-based triple therapy in patients with duodenal ulcer hemorrhage did not result in significant reduction in further bleeding episodes, although a trend was seen for the group that was given triple therapy. On the other hand, posttreatment H. pylori status was found to be an independent predictor of bleeding recurrence.     

Prospective multicentre study of risk factors associated with delayed healing of recurrent duodenal ulcers (RUDER). RUDER Study Group.

Risk factors for delayed duodenal ulcer healing during treatment with ranitidine (300 mg daily) were examined in a multicentre German study of 1923 patients with endoscopically proved, recurrent duodenal ulceration. Healing rates, per protocol, were 39.5% at two weeks, 70.9% at four weeks, and 93.2% at eight weeks. Prospective testing of five, predefined risk factors indicated that smoking (p = 0.0039) was associated with a decreased healing rate at two weeks. Frequent prior recurrence (p = 0.464), a heavy physical workload (p = 0.145), and psychological stress (p = 0.062) were not associated with a decreased healing rate and there were too few patients at risk to allow assessment of the effect of regular NSAID intake. Exploratory analysis identified prior slow healing, a large ulcer, multiple ulcers, and prior ulcer complications, in addition to smoking, as markers of slow healing. In the absence of these risk factors, the mean healing time was 3.3 weeks (95% confidence interval 3.0, 3.5), rising to 3.7 weeks (3.5, 3.9) for one, 4.4 weeks (4.1, 4.7) for two, and 5.1 weeks (4.5, 5.6) for three to five risk factors. Delayed duodenal ulcer healing is associated with multiple factors whose effect is cumulative; for patients with two or more of five easily identified risk factors, more than four weeks' treatment with a histamine H2 receptor antagonist is required to achieve ulcer healing.     

Famotidine for healing and maintenance in nonsteroidal anti- inflammatory drug-associated gastroduodenal ulceration

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulceration. How to manage patients with NSAID-associated ulcers is a common clinical dilemma. High-dose famotidine in the healing and maintenance of NSAID-associated gastroduodenal ulceration was therefore evaluated. METHODS: One hundred four patients with rheumatoid or osteoarthritis who had gastroduodenal ulceration received famotidine, 40 mg twice daily. Sixteen patients stopped and 88 continued their NSAID treatment. Ulcer healing was assessed endoscopically at 4 and 12 weeks. Seventy-eight NSAID users with healed ulcers were then randomized to receive 40 mg twice daily famotidine or placebo and underwent endoscopy at 4, 12, and 24 weeks. RESULTS: Cumulative ulcer healing rates at 12 weeks were 89.0% (95% confidence interval [CI], 82.3%-95.7%) for patients who continued NSAID treatment and 100% (95% CI, 82.9%-100.0%) for those who stopped. The subsequent estimated cumulative gastroduodenal ulcer relapse over 6 months for NSAID users who took placebo was 53.5% (95% CI, 36.6%- 70.3%). This was reduced to 26.0% (12.1%-39.9%) in patients taking famotidine (P = 0.011). CONCLUSIONS: High-dose famotidine is effective ulcer healing therapy in patients who stop or continue NSAID treatment and significantly reduced the cumulative incidence of gastroduodenal ulcer recurrence compared with placebo when given as maintenance therapy. (Gastroenterology 1997 Jun;112(6):1817-22)     

Safety of Ranitidine Maintenance Treatment of Duodenal Ulcer

During maintenance treatment with nocturnal ranitidine (150 mg) for 1 year, 38% of duodenal ulcers relapsed. Twenty-one patients whose ulcers remained healed after maintenance treatment for 1 year continued to receive ranitidine (150 mg at night) for a further year, while 26 patients with healed ulcers received placebo in a randomized double-blind study. The rate of recurrence of duodenal ulcers during the 2nd year of follow-up study was 18% in ranitidine-treated individuals and 87% in those receiving placebo. The ulcer recurrences of patients receiving ranitidine tended to be asymptomatic and were clinically mild in the rest. Recurrences in patients receiving placebo were usually symptomatic and significantly more likely to be associated with bleeding. We conclude that ulcers that remain healed after 1 year's maintenance treatment with ranitidine tend to remain healed if maintenance treatment is continued. Moreover, this type of continuous treatment of duodenal ulcer is clinically safer than no treatment of the ulcer disease.     

Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study.

OBJECTIVE: To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease. DESIGN: Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials. SETTING: A Veterans Affairs hospital. PARTICIPANTS: A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy. INTERVENTION: Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. MEASUREMENTS: Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years. RESULTS: The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.     

Safety of ranitidine maintenance treatment of duodenal ulcer

During maintenance treatment with nocturnal ranitidine (150 mg) for 1 year, 38% of duodenal ulcers relapsed. Twenty-one patients whose ulcers remained healed after maintenance treatment for 1 year continued to receive ranitidine (150 mg at night) for a further year, while 26 patients with healed ulcers received placebo in a randomized double-blind study. The rate of recurrence of duodenal ulcers during the 2nd year of follow-up study was 18% in ranitidine-treated individuals and 87% in those receiving placebo. The ulcer recurrences of patients receiving ranitidine tended to be asymptomatic and were clinically mild in the rest. Recurrences in patients receiving placebo were usually symptomatic and significantly more likely to be associated with bleeding. We conclude that ulcers that remain healed after 1 year's maintenance treatment with ranitidine tend to remain healed if maintenance treatment is continued. Moreover, this type of continuous treatment of duodenal ulcer is clinically safer than no treatment of the ulcer disease.     

Prevention of duodenal ulcer occurrence. Double-blind comparison of ranitidine and cimetidine

We compared ranitidine and cimetidine in maintenance therapy to prevent duodenal ulcer recurrence over a period of 24 months. Endoscopic examination at the end of 12 months showed that the ulcers of 26 of 31 patients (84%) on ranitidine in a dose of 150 mg remained healed and of 10 of 13 (77%) patients on cimetidine in a dose of 400 mg at night remained healed. Thirty-four patients continued in an open evaluation of ranitidine in a dose of 150 mg at night for a further 12-month period, and during this time there were four further recurrences. Life table estimates of duodenal ulcer recurrence during the 2-year period showed no significant difference between the two forms of treatment.     

Histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine

Abstract We investigated the relationship between histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine for 4 weeks. The healing rates, 92.5 and 72.4% in omeprazole-treated and cimetidine-treated groups, respectively, showed no significant difference between groups ( P > 0.05). Histologically, the regenerating mucosa of healed ulcer was divided into three categories: good, fair and poor patterns. Of the healed cases, 22 (59.5%) of 37 omeprazole-treated and 12 (28.6%) of 42 cimetidine-treated ulcers achieved a good pattern, showing significant difference between groups ( P = 0.01). The recurrence rate at 3 months showed statistically significant difference ( P < 0.05) between two groups: 5.4% in omeprazole-treated and 23.8% in cimetidine-treated patients. During the period between 3 and 6 months after healing, the difference in recurrence rate between omeprazole-treated and cimetidine-treated groups was statistically not significant (12.5% and 25%, respectively, P > 0.05), though the cumulative recurrence rate at 6 months showed a significant difference between groups (17.6% vs 44.7%, P = 0.027). All the recurrent cases of both groups had a fair or poor pattern of regenerating mucosa. The difference in recurrence rate was statistically significant between the healed ulcers with a good pattern and that with a fair or poor patterns both at 3 months and between 3 and 6 months after healing ( P > 0.001 in each). We concluded that better histological maturity of regenerating mucosa may contribute to the lower early recurrence in omeprazole-treated cases than in cimetidine-treated cases.     

Oral tripotassium-dicitratobismuthate in gastric and duodenal ulceration

One hundred ambulant outpatients with active, endoscopically proven peptic ulceration entered a double-blind trial of either tripotassium-dicitratobismuthate or placebo. Thirty-four patients had gastric ulceration, 56 had duodenal ulceration, three had both gastric and duodenal ulcers, and two had stomal ulceration. Five patients with gastric ulceration were withdrawn from the trial. Three patients with both gastric and duodenal ulceration and two patients with stomal ulceration were excluded from statistical analysis. After 28 days of tripotassium-dicitratobismuthate 94% of gastric ulcer patients had significant endoscopic healing (P less than 0.01). Although 75% of duodenal ulcers healed after 28 days of tripotassium-dicitratobismuthate, this was not statistically significant because of a 60% rate of healing with placebo. Tripotassium-dicitratobismuthate produced a significantly quicker symptomatic response in duodenal ulcer patients (P less than 0.01). No serious side effects were recorded, and patient acceptability was high. It is concluded that tripotassium-dicitratobismuthate is an effective agent for promoting gastric ulcer healing and for symptomatic relief in duodenal ulceration.     

Significance of Helicobacter Pylori Infection in Human Peptic Ulcers

Abstract: Experimental studies have suggested that the continuous administration of 0.02% NH, solution, induced by Helicobacter pylori (H, Pylori), leads to a glandular atrophy of the gastric mucosa, and adversely affects healing of acetic acid ulcers in rats, because of the suppression of cell kinetics of the regenerative epithelial cells and connective tissues at ulcer margins. To visualize the distribution of H. pylori in human gastric mucosa, a phenol red dye spraying endoscopy was performed in 45 patients with gastric ulcers, and 43 patients with duodenal ulcers, who were medicated with a full dose of H₂-blocker until ulcer healing, and with half doses thereafter. In the H. pylori negative cases, 8 (88.9%) of 9 gastric ulcers healed within 3 months after medication, with no relapse discernible up to 6 months after healing of the preceding ulcer. The relapse rate was 25% up to 12 months after ulcer healing. In contrast, only 22 (66.1%) of 36 gastric ulcers healed within 3 months after medication in the H. pylori positive cases. The relapse rate was 12.5% up to 3 months, 30.4% UP to 6 months and 63.6% up to 12 months after ulcer healing. In addition, all 6 duodenal ulcers healed within 2 months after medication in the H. pylori negative cases, with no relapse discernible up to 12 months after healing of the preceding ulcer. In contrast, in the H. pylon positive cases, 20 (53.1%) of 37 duodenal ulcers healed within 2 months, and the relapse rate was 14.3%, 33.3%, and 66.7% up to 3, 6 and 12 months respectively after healing of the preceding ulcer. These data suggest that H. pylori is likely to interfer with ulcer healing, and promotes peptic ulcer relapse.     

Morphological and Functional Evaluation of Gastric Ulcer Healing and Recurrence by Endoscopic Ultrasonography

Abstract: The aim of this study was the evaluation of gastric ulcer healing and recurrence, from the viewpoints of morphology and function, by means of endoscopic ultrasonography (EUS). We determined ulcer depth by EUS and quantified ulcer size in EUS images. In addition, we measured the total gastric juice acid content after fasting and the macromolecular glycoprotein weight in antral biopsies. First, we examined 22 patients receiving initial therapy during the active ulcer stage. Fourteen of these patients were reexamined after healing. The ulcer area diminished significantly, as did the total acid content, during the scarring stage. Then, another 22 patients on maintenance therapy were followed for recurrence over a 10 month period. The recurrence rate in UI-IV ulcers was significantly higher than those in UI-II or III ulcers. The ulcer area was greater and the macromolecular glycoprotein content lower in patients experiencing recurrence. In conclusion, morphological and functional factors (ulcer depth and ulcer area; total acid content and macromolecular glycoprotein weight), which could be assessed easily and simultaneously using an EUS fiberscope with a biopsy channel, were useful for evaluating gastric ulcer healing and recurrence.     

The influence of severe bulb deformity on duodenal ulcer relapse

In order to evaluate the prognostic role of duodenal bulb deformation in the recurrence of peptic ulcer, duodenal bulb morphology and the complete healing of duodenal ulcer were endoscopically evaluated in sixty patients, who were subsequently allocated at random to either maintenance therapy with ranitidine or no treatment. Endoscopic checkups were done at regular intervals, up to the first ulcer recurrence. As expected, long-term ranitidine treatment significantly reduced the relapse rate (12 month cumulative relapse rate was 32% versus 86% in the untreated). A set of prognostic factors which might interfere with this result (sex, age, alcohol consumption, history of ulcerous relatives, duration of the disease, previous H2-blocking treatment, previous complications, smoking and morphology of the duodenal bulb) were evaluated by multivariate analysis using the Cox regression model. Only duodenal bulb morphology appeared to have any independent prognostic value. In the untreated group ulcer recurrence seemed to occur earlier (median relapse time = 2 months) in the patients with severe non-stenosing bulb deformity, and later in those with normal or mildly deformed bulb (median relapse time = 8 months); ranitidine treatment delayed relapse in deformed bulb patients (median relapse time = 14 months) and almost eliminated it in those with normal duodenal bulb morphology. No association was found between the presence of duodenal bulb deformity and the above-mentioned covariates. Our study confirms the primary importance of anti-H2 treatment and suggests that anatomical characteristics of the duodenal bulb also influence the occurrence of ulcer relapse.     

Cost-effectiveness of cimetidine maintenance therapy in chronic gastric and duodenal ulcer

The effects of cimetidine maintenance therapy on the socioeconomic life of patients with peptic ulcers in the 3 years after healing and the extent to which treatment was cost-effective were studied. Three hundred eleven patients with healed ulcers (184 gastric, 127 duodenal) were studied for periods of up to 3 years; 261 patients (152 gastric ulcer, 109 duodenal ulcer) completed the 3-year follow-up. Cimetidine (400 mg at night) was compared with placebo in a double-blind, randomized prospective study. Intention-to-treat analysis was used. In the placebo group, the major costs of ulcer disease in gastric ulcer patients were attributable to endoscopic procedures and absenteeism; in duodenal ulcer patients, the major costs were endoscopic procedures, absenteeism, and surgery. Cimetidine was cost-effective in both gastric ulcer and duodenal ulcer patients in the first 2 years after healing. Over the 3-year period it was also cost-effective, but no benefit was seen in the third year.