Omeprazole in H2 receptor antagonist-resistant reflux esophagitis

We conducted a retrospective review of 25 patients with severe reflux esophagitis treated with omeprazole because of failure of H2 receptor antagonists to heal their esophagitis. Prior to beginning omeprazole (40 mg/day), all patients were on H2 antagonists for at least 9 months and still had endoscopic evidence of longitudinal (grade II) or circumferential (grade III) distal esophageal ulceration. Omeprazole therapy brought about complete endoscopic healing in 24 of 25 patients (96%). Twenty-three of 24 healed patients were then restarted on H2 antagonists as maintenance therapy. Repeat endoscopy was performed if symptoms recurred. Fourteen of 24 patients (58%) had recurrence of endoscopic esophagitis documented between 26 and 300 days from the time of starting maintenance therapy. Two of these 14 patients opted for antireflux surgery, whereas the remaining 12 were once again given omeprazole, which again resulted in symptom resolution in all patients. These data suggest that most patients with H2 receptor antagonist-resistant ulcerative esophagitis cannot be successfully maintained on H2 antagonists even after the ulcers have been healed with omeprazole. Further studies are required to determine the role of omeprazole compared to other treatments in the long-term maintenance therapy of these patients.     

Spectrum of esophageal disorders in children with chest pain

The charts of 83 children with chest pain who underwent esophageal manometry followed by esophagogastroscopy were reviewed. Forty-seven (57%) had normal esophageal histology and normal motility (group I). Esophagitis and normal motility were demonstrated in 15 children (group II), normal esophageal histology and esophageal dysmotility in 13 (group III), and both esophagitis and abnormal motility in 8 (group IV). Diffuse esophageal spasm and achalasia were the most common motility disorders identified (in seven and four patients, respectively). The presence and duration of symptoms, the age, and the gender were not different among the four patient groups. After six months of H₂-receptor blockade, 12 of 15 group II patients were asymptomatic, whereas a significantly smaller percentage (five of 18) of patients with abnormal esophageal motility responded to esophageal dilation or treatment with calcium channel blockade, H₂-receptor antagonist, and/or prokinetic agents (P<0.01). These data suggest that the evaluation of children with chest pain should include esophageal motility testing and esophagoscopy, even in the absence of other gastrointestinal-associated symptoms, and that while treatment of esophagitis results in resolution of symptoms, motility disorders were relatively refractory to therapy.     

Maintenance therapy for erosive esophagitis in children after healing by omeprazole: is it advisable?

OBJECTIVES: To evaluate the efficacy of acid-suppressive maintenance therapy for gastroesophageal reflux disease (GERD) in children, after the healing of reflux esophagitis. METHODS: Forty-eight children (median age 105 months, range 32-170) with erosive reflux esophagitis were initially treated with omeprazole 1.4 mg/kg/day for 3 months. Patients in endoscopic remission were assigned in a randomized, blinded manner by means of a computer-generated list to three groups of 6-month maintenance treatment: group A (omeprazole at half the starting dose, once daily before breakfast), group B (ranitidine 10 mg/kg/day, divided in two doses), and group C (no treatment). Endoscopic, histological, and symptomatic scores were evaluated at: T0, enrollment; T1, assessment for remission at 3 months after enrollment (healing phase); T2, assessment for effective maintenance at 12 months after T0 (3 months after the completion of the maintenance phase). Relapse was defined as the recurrence of macroscopic esophageal lesions. After the completion of the maintenance phase, patients without macroscopic esophagitis relapse were followed up for GERD symptoms for a further period of 30 months. RESULTS: Of 48 initially treated patients, 46 (94%) healed and entered the maintenance study. For all patients, in comparison to T0, the histological, endoscopic, and symptomatic scores were significantly reduced both at T1 and T2 (P<0.0001, for each). No significant difference was found in these three scores, comparing group A, B, and C at T1 and T2. A relapse occurred in one patient only, who presented with macroscopic esophageal lesions at T2. Three months after the completion of the maintenance phase, 12 (26%) patients complained of symptoms sufficiently mild to discontinue GERD therapy, excluding the patient who showed macroscopic esophagitis relapse. Three of 44 (6.8%) patients reported very mild GERD symptoms within a period of 30 months after maintenance discontinuation. CONCLUSIONS: Our pediatric population showed a low rate of erosive esophagitis relapse and GERD symptom recurrence long term after healing with omeprazole, irrespective of the maintenance therapy.     

Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%,P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.     

Treatment of erosive reflux esophagitis resistant to H2-receptor antagonist therapy

Fifty-four patients with endoscopically documented therapy-resistant erosive reflux esophagitis were treated with lansoprazole, a new proton pump inhibitor, for up to 12 weeks. Prior to entry, all had remained unhealed after treatment with at least two histamine₂-receptor antagonists, at therapeutic doses or higher, for at least 12 weeks. Patients were randomized to receive either 30 or 60 mg lansoprazole once daily. Endoscopy was performed and symptoms assessed at weeks 2, 4, 6, 8, and 12. Fifty-nine percent of the 50 evaluable patients were healed (ie, no evidence of erosions) after only two weeks of lansoprazole. Cumulative endoscopic healing rates were 82% and 92% by week 4 and week 8, respectively, and the two doses were equally effective in healing. The 30- and 60-mg doses effected a decrease in the overall symptom score from 5.30 and 4.85 to 2.35 and 1.67, respectively, by the final treatment visit (P=0.001). No clinically significant adverse events or changes in laboratory parameters were observed, and no patients withdrew prematurely from the study. This study demonstrates that lansoprazole therapy is highly effective in healing erosive reflux esophagitis resistant to therapy with histamine H₂-receptor antagonists.Supported by a grant from TAP Pharmaceuticals Inc., Deerfield, Illinois.     

Comparison of four proton pump inhibitors for the short-term treatment of esophagitis in elderly patients

AIM: To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients.METHODS: A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk: (1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d; (3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d. Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated.RESULTS: Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole = 93.5% (P = 0.04 vs omeprazole) and 90.0% (P = 0.02 vs omeprazole), rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates: 81.8% vs 100%, 100% and 100%, respectively, P = 0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001)and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P < 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P < 0.05) in decreasing epigastric pain.CONCLUSION: In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms. H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI.     

Omeprazole in the treatment of patients with severe reflux oesophagitis not responding to H2-receptor antagonists and ineligible for surgery

In 42 patients (25 men, 17 women, mean age 62 years) with severe erosive or ulcerative oesophagitis not responding to H2-receptor antagonist treatment over at least 3 months and ineligible for surgery, omeprazole was administered at an initial dose of 40 mg/day, subsequently reduced to 20 mg after healing of the lesions. Patients had monthly clinical, endoscopic, histological and laboratory assessment over the healing period, then were reevaluated 3-monthly over one year, then 6-monthly, during the maintenance treatment. Stages of oesophagitis were based on the Savary-Miller classification, modified for stage I (erosions must be present). With 40 mg omeprazole, healing was observed in 71%, 83% and 90% of the patients after 1, 2 and 3 months of treatment, respectively. After one month of treatment, a complete healing was less frequently observed in patients with stage IV oesophagitis pre-trial (55%) than in the patients with stages I, II and III pre-trial (90%) (p less than 0.05). Ninety per cent of the patients healed at one month were asymptomatic whereas 50% of the patients with incomplete healing still had symptoms, most often dysphagia, rarely heartburn. Maintenance treatment with 20 mg was sufficient in most patients, with a probability of remaining healed of 69% from 9 to 24 months after starting this dosage. In 9 patients with Barrett's oesophagus, the lengths of the circumferential metaplasia were found to be reduced after one year of treatment compared to pre-trial lengths (p less than 0.005). There was no further significant reduction of length after 2 years of treatment. Fasting gastrin was increased in most of the patients, although great inter-patient variability was observed; 50% of the patients had levels not exceeding 5 times the upper limit of normal. There was no consistent increase of enterochromaffin-like cell density in 29 patients investigated up to nearly 2 years of omeprazole administration. The treatment was well tolerated. By inducing a profound and sustained inhibition of acid secretion, as confirmed by pH monitoring, omeprazole promotes healing of the lesions of severe oesophagitis and prevents recurrence of lesions and symptoms. Omeprazole is therefore a valuable treatment for patients ineligible for surgery, particularly in the elderly.     

Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study

To determine the long-term efficacy, safety, and toxicity of omeprazole, we studied 40 patients with Zollinger-Ellison syndrome given omeprazole for 6-51 mo (median 29). The mean daily dose of omeprazole required to control gastric acid secretion was 82 +/- 31 mg. Thirty-one patients required omeprazole once per day. In 9 patients acid output was not controlled by 120 mg once per day, but was controlled by 60 mg every 12 h. The daily dose of omeprazole correlated with the previous dose of histamine H2-receptor antagonist (r = 0.89, p less than 0.001), basal acid output (r = 0.43, p less than 0.01), and maximal acid output (r = 0.39, p less than 0.02) but not with serum concentration of gastrin (r = -0.32). Increases in the dose of omeprazole were required in 9 patients. Twenty-nine patients had mild peptic symptoms with acid outputs less than 10 mEq/h while taking histamine H2-receptor antagonists. Symptoms resolved completely in 23 patients and partially in 3 when taking omeprazole. Omeprazole prevented mucosal disease in all patients including 17 in whom histamine H2-receptor antagonists had produced only partial resolution despite acid output being less than 10 mEq/h and in those with symptoms during omeprazole therapy. Omeprazole therapy was not associated with any significant side effects, nor with any evidence of hematologic or biochemical toxicity. Serum concentrations of gastrin did not change significantly during therapy. In 6 patients treated with omeprazole for 1 yr there was no change in basal or maximal acid output. In all patients, gastric morphology and histopathology demonstrated no evidence of gastric carcinoid formation. These results demonstrate that with long-term treatment of up to 4 yr, omeprazole is safe, with no evidence of hematologic, biochemical, or gastric toxicity. Furthermore, omeprazole remained effective, with only 23% of patients requiring an increase in dose, and continued to control symptoms in patients who had not been entirely symptom-free despite high doses of histamine H2-receptor antagonists. Omeprazole is now the drug of choice in patients with Zollinger-Ellison syndrome.     

Healing and relapse of severe peptic esophagitis after treatment with omeprazole

We have studied the response of erosive or ulcerative esophagitis to treatment with omeprazole and its subsequent relapse on cessation of therapy in 196 patients. In the first phase of the study omeprazole (20 or 40 mg daily) was compared with placebo in 64 patients. After 4 wk there was endoscopic healing in 81% (25 of 31) of omeprazole-treated patients and in only 6% (2 of 32) of placebo-treated patients. Endoscopic healing of esophagitis was accompanied by symptom relief and histologic healing of ulceration. In the second (dose finding) phase a further 132 patients were randomized to omeprazole (20 or 40 mg daily) and endoscopic healing was assessed. In patients with the mildest grade of ulcerative esophagitis (grade 2), healing occurred at 4 wk in 87% receiving 20 mg and in 97% receiving 40 mg. In patients with grade 3 esophagitis, 67% (20 mg) and 88% (40 mg) were healed. Less than half the patients with grade 4 esophagitis (Barrett's ulcers or confluent ulceration) healed with either 20 mg (48%) or 40 mg (44%). Regression analysis in the 164 omeprazole-treated patients showed no evidence that healing was influenced by factors other than severity of esophagitis at entry and omeprazole dose. In phase 3 of the study the rate of endoscopic relapse was determined in 107 endoscopically healed patients after stopping omeprazole. Erosive or ulcerative esophagitis recurred in 88 of 107 (82%) by 6 mo. Neither initial dose, grade of esophagitis, nor smoking was shown to influence relapse rate. Omeprazole is a highly effective treatment for peptic esophagitis. The 40-mg/day dosage produces endoscopic healing slightly more quickly than the 20-mg/day dosage, and the initial endoscopic gradings are of prognostic value. Relapse occurs rapidly when treatment is stopped.     

Effect of omeprazole on the course of associated esophagitis and laryngitis

Esophagitis has increasingly been implicated as a cause of chronic laryngitis and there is some evidence that gastro-esophageal reflux disease (GERD) is more common in patients with laryngitis. The aim of this study was to evaluate whether patients with esophagitis and laryngitis responded to treatment with omeprazole. Of 74 consecutive patients with endoscopically proven GERD, 21 had laryngitis. These 21 patients with associated esophagitis and chronic laryngitis were treated for 4 weeks with omeprazole 40 mg per day. After 2 weeks of treatment and at the conclusion of the study, 2 weeks later, esophagoscopy and laryngoscopy were performed and the patients responded to a questionnaire on their symptoms. The follow-up period was 1 year. Twenty-one of the 74 patients (28.4%) had esophagitis (grade I,n=12; grade II,n=9) and associated laryngitis (grade I,n=14; grade II,n=7). The severity of the esophagitis accorded with the severity of the laryngitis. After 2 weeks' treatment with omeprazole, both the esophageal and the laryngeal symptoms had improved in all 21 patients. Endoscopically, the healing rates were 62% for esophagitis and 33.3% for laryngitis. At the end of the study period, at 4 weeks, all patients were symptom-free and the esophagitis and laryngitis had healed completely. No patient suffered from drug-induced side effects. Patients with associated laryngitis and esophagitis should be given adequate anti-reflux therapy. Both the laryngeal and esophageal symptoms improved with the omeprazole treatment, suggesting that reflux was the underlying etiology.     

Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) in primary care practice presents symptomatically, and resources to distinguish promptly between erosive esophagitis and endoscopy-negative reflux disease (ENRD) are limited. It is therefore important to determine the roles of proton pump inhibitors and histamine-2-receptor antagonists for first-line symptom-based therapy in patients with erosive esophagitis and ENRD. The aim of this study was to compare pantoprazole 40 mg once daily versus nizatidine 150 mg b.i.d. in a mixed GERD patient population with ENRD or erosive esophagitis (Savary-Miller grades 1-3). METHODS: A 4-wk randomized, double-blind, parallel-group, multicenter study conducted in Canada. Eligible patients had experienced GERD symptoms > or = 4 times weekly for > 6 months. Patients were randomized to pantoprazole 40 mg once daily or nizatidine 150 mg b.i.d.. Endoscopy was performed before randomization and after 4 wk of therapy. RESULTS: Of 220 patients randomized to therapy, 208 were available for a modified intent-to-treat analysis. Erosive esophagitis was present in 125 patients; 35 patients were Helicobacter pylori positive. There was complete symptom relief after 7 days of therapy in 14% of patients on nizatidine and in 40% of those on pantoprazole (p < 0.0001), and after 28 days of treatment in 36% and 63% of patients, respectively (p < 0.0001). After 28 days of treatment, adequate heartburn control was reported by 58% of the nizatidine group and in 88% of the pantoprazole (p < 0.0001); erosive esophagitis healing rates were 44% for nizatidine and 79% for pantoprazole (p < 0.001). Rescue antacid was needed by a greater number of patients using nizatidine than of those using pantoprazole (p < 0.001). H. pylori infection was associated with an increased probability of erosive esophagitis healing. CONCLUSIONS: Pantoprazole once daily was superior to nizatidine b.i.d. in producing complete heartburn relief in a mixed population of GERD patients and in achieving erosion healing. The proportions of patients with complete symptom relief were greater with pantoprazole after 7 days of therapy than with nizatidine after 28 days. The present study data suggest that pantoprazole is a highly effective first-line therapy for the management of gastroesophageal reflux disease in a primary care practice setting.     

24-Hour Intragastric Acidity and Plasma Gastrin during Long-Term Treatment with Omeprazole or Ranitidine in Patients with Reflux Esophagitis

The reduction in intragastric acidity and the subsequent increase in plasma gastrin were compared during long-term treatment with either omeprazole or ranitidine in 19 patients with erosive reflux esophagitis. The patients received 40 mg omeprazole in the morning or 300 mg ranitidine twice daily. After healing, half the dose was given as maintenance treatment for 1 year. Intragastric acidity and plasma gastrin were measured 24 h before entry and monthly with the high dose and after 1, 6, and 12 months with the low dose. Omeprazole reduced intragastric acidity more effectively than ranitidine (p < 0.001). This difference in efficacy was more pronounced during the daytime. Plasma gastrin increased more after omeprazole than after ranitidine (p < 0.01), and both drugs showed a normal postprandial response and approached fasting levels before the next dose. During long-term treatment with 20 mg omeprazole in the morning no progressive alterations were observed in 24-h intragastric acidity or plasma gastrin.     

Omeprazole or ranitidine in the treatment of reflux esophagitis. Results of a double-blind, randomized, Scandinavian multicenter study

One hundred and fifty-two patients with endoscopically verified erosive and/or ulcerative esophagitis entered a double-blind, randomized study comparing 20 mg omeprazole given once daily and ranitidine 150 mg twice daily. The efficacy and safety of 4 to 8 weeks' treatment were studied. Macroscopic healing of esophagitis was defined as complete epithelialization of all esophageal erosive and/or ulcerative lesions. One hundred and forty-four patients completed the first 4 weeks of treatment in accordance with the protocol. The healing rate was 67% in the omeprazole group and 31% in the ranitidine group (p less than 0.0001). The corresponding figures after 8 weeks' treatment were 85% and 50%, respectively (p less than 0.0001). The higher healing rate for omeprazole was also accompanied by a significantly faster and more substantial improvement in reflux symptoms. In the patient's own overall evaluation of symptoms, these had resolved in 51% of the omeprazole-treated patients already at the end of the 1st week of treatment, compared with 27% of those given ranitidine (p = 0.009). Both omeprazole and ranitidine were well tolerated, and there were no adverse events or clinically significant changes in the laboratory values attributable to the trial medication.     

Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa

BACKGROUND & AIMS: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years). METHODS: Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus. RESULTS: In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients. CONCLUSIONS: Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.     

Failure of Initial 24-Hour Esophageal pH Monitoring to Predict Refractoriness and Intractability in Reflux Esophagitis

Prolonged esophageal pH monitoring is considered to be the most sensitive and specific test for the diagnosis of gastroesophageal reflux disease (GERD). However, the role of pH monitoring in predicting the clinical and endoscopic response of reflux esophagitis is not well defined. In this study, 106 patients with moderate to severe symptoms of GERD and esophagitis (grades 0-IV) by endoscopy were initially studied by ambulatory esophageal pH monitoring, and their clinical response to standard H2 antagonist therapy was monitored at 8 wk. Refractory patients were defined as those who failed to heal and/or had intractable reflux symptoms after 8 wk of H2 antagonist therapy, and who required continuous therapy with higher doses of H2 antagonists, addition of prokinetic agents, or omeprazole. There was a positive correlation (r = 0.89) between endoscopic severity of esophagitis upon entry into the study and refractoriness to standard medical therapy. However, there were no differences in the various pH parameters analyzed between the 58 patients who responded and the 48 patients who were refractory to medical therapy, regardless of the endoscopic grading of their esophagitis. We conclude that 24-h ambulatory esophageal pH monitoring does not predict refractoriness of reflux esophagitis to standard therapy. The decision for more aggressive methods of treatment probably requires assessment of symptomatic and endoscopic response after 8 week standard H2 antagonist therapy.     

24-hour intragastric acidity and plasma gastrin during long-term treatment with omeprazole or ranitidine in patients with reflux esophagitis

The reduction in intragastric acidity and the subsequent increase in plasma gastrin were compared during long-term treatment with either omeprazole or ranitidine in 19 patients with erosive reflux esophagitis. The patients received 40 mg omeprazole in the morning or 300 mg ranitidine twice daily. After healing, half the dose was given as maintenance treatment for 1 year. Intragastric acidity and plasma gastrin were measured 24 h before entry and monthly with the high dose and after 1, 6, and 12 months with the low dose. Omeprazole reduced intragastric acidity more effectively than ranitidine (p less than 0.001). This difference in efficacy was more pronounced during the daytime. Plasma gastrin increased more after omeprazole than after ranitidine (p less than 0.01), and both drugs showed a normal postprandial response and approached fasting levels before the next dose. During long-term treatment with 20 mg omeprazole in the morning no progressive alterations were observed in 24-h intragastric acidity or plasma gastrin.     

Current trends in the pharmacotherapy for gastroesophageal reflux disease.

Medical therapy for gastroesophageal reflux disease should entail a multistep approach. After life-style changes, many patients will require histamine2 receptor antagonists in conventional doses with repeated therapeutic courses, if not continuous maintenance. Prokinetic agents are potentially useful in those patients with impaired motor function of the esophageal or gastric smooth muscle. Combination therapy with histamine2 receptor antagonists and prokinetic agents or sucralfate provides modest healing benefit, if any, over that by histamine2 receptor antagonists alone. For patients with more severe refractory disease, omeprazole has provided unequaled healing rates and accelerated symptomatic relief. High-dose (twofold or more standard dose) histamine2 receptor antagonist therapy may also heal high-grade esophagitis, but the reported experience is small. After healing is achieved, an attempt should generally be made to "step down" therapy to standard-dose histamine2 receptor antagonist as maintenance. Finding the least amount of drug to control symptoms and maintain the integrity of the esophageal mucosa would minimize cost and potential long-term risk.     

Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study.

Two hundred thirty patients with reflux symptoms and endoscopically proven erosive esophagitis were enrolled from 15 U.S. centers into a randomized, double-blind, dose-ranging study comparing placebo with omeprazole, 20 or 40 mg given once daily in the morning. Esophagitis grade 2 was present in 44% of patients, grade 3 in 37% of patients, and grade 4 in 19% of patients. Endpoints, defined as complete relief of heartburn and complete esophageal mucosal healing, were assessed after 4 and 8 weeks of treatment. Both omeprazole doses were significantly superior to placebo in complete endoscopic healing. After 8 weeks of treatment, 73.5% of patients in the 20-mg omeprazole group and 74.7% in the 40-mg omeprazole group, compared with 14.0% in the placebo group, had complete healing of the esophageal mucosa. At the end of the study, complete relief of daytime heartburn was obtained in 79.5% of patients in the 20-mg omeprazole group, 81.6% in the 40-mg omeprazole group, and 37.2% in the placebo group (P less than or equal to 0.05). Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05). The median time to complete relief of daytime and nighttime heartburn occurred earlier in the 40-mg group than in the 20-mg group (9 vs. 17 days and 9 vs. 20 days, respectively); however, these differences were not statistically significant. Relief of acid regurgitation and dysphagia also occurred earlier in the 40-mg group. Omeprazole was well tolerated in this group of patients. No unexpected adverse experiences occurred. The results of this study confirm those of six multicenter, international trials in which omeprazole in doses of 20-60 mg provided a degree of esophageal mucosal healing and complete relief of reflux symptoms superior to any other medical treatment.     

Therapy with omeprazole in patients with peptic ulcerations resistant to extended high-dose ranitidine treatment

94 patients with peptic ulcerations of duodenum, stomach, and esophagus, who did not respond to 3 or more months high-dose (450 or 600 mg) treatment with ranitidine, were treated orally with 40 mg omeprazole daily. After healing all patients were offered long-term maintenance therapy with the same dose for 5 years. In 75 patients the peptic ulcerations healed within 4 weeks, in 13 patients within 8 weeks, and in 3 patients only after an increase to 60 mg omeprazole daily. In 3 patients the ulcers did not heal. So far 83 patients have entered long-term maintenance therapy. 59 of these patients are on the drug between 1 and 4 years. During maintenance therapy with 40 mg omeprazole no relapses have occurred up to now as demonstrated by endoscopy and no drug-related adverse effects were observed. Routine laboratory tests remained without significant changes in all patients including 18 patients with concomitant liver cirrhosis. Serum gastrin levels were already elevated during the initial high-dose ranitidine treatment (106 +/- 15.4 pg/ml). 4 weeks after the start of omeprazole treatment serum gastrin levels rose to 4 times normal levels (195 +/- 28 pg/ml). Thereafter, no further increase in serum gastrin was observed even up to 4 years of continuous observation. It is therefore concluded that omeprazole is highly effective in healing ranitidine-resistant peptic ulcerations and that omeprazole maintenance therapy with 40 mg omeprazole is safe during the time observed and highly effective in the prevention of ulcer recurrence.     

Prevention of Relapse of Reflux Esophagitis after Endoscopic Healing: The Efficacy and Safety of Omeprazole Compared with Ranitidine

Ninety-eight patients with erosive and/or ulcerative esophagitis unhealed after at least 3 months' treatment with standard doses of cimetidine (≥1200mg daily) or ranitidine (≥300 mg daily) were primarily included in an acute healing phase study, and 51 were allocated to 40 mg omeprazole once daily and 47 to 300 mg ranitidine twice daily. After 12 weeks of treatment, 46 (90%) patients given omeprazole were healed, compared with 22 (47%) allocated to ranitidine. Healed patients were then given maintenance treatment with either 20 mg omeprazole once daily or 150 mg ranitidine twice daily for 12 months. Plasma gastrin was determined and gastric mucosal biopsy specimens were obtained during the entire study to assess the structure of the exocrine and endocrine cell populations of the oxyntic mucosa. Sixty-seven per cent of the total number of patients randomized to omeprazole were maintained in clinical and endoscopic remission throughout the 12-month study period as compared with only 10% among those given ranitidine (p < 0.0001). After 4 weeks of omeprazole treatment basal gastrin levels were slightly increased, with a 95% confidence interval for the change of from 8.6 to 16.9pmol/l. No further increase in basal gastrin levels was observed during the ensuing study months. No significant histopathologic lesion was found in the oxyntic gland mucosa. In conclusion, omeprazole was far superior to ranitidine in preventing recurrence, a goal achieved without adverse events and significant abnormalities in the oxyntic mucosal exocrine or endocrine cells but with a moderate increase in basal gastrin levels.