OMEPRAZOLE AND COMPLICATED GASTRO-OESOPHAGEAL REFLUX DISEASE

Abstract Suppression of acid secretion with omeprazole is highly effective for the healing of oesophagitis. The aims of the present study were to determine whether recovery of gastro-oesophageal reflux disease in patients with stricture improves dysphagia and decreases the dilatation need and to compare the efficacy of omeprazole versus H₂-receptor antagonists. Thirty-eight patients with peptic stricture (grade IV oesophagitis) and erosive oesophagitis underwent endoscopic dilatation and were randomized to omeprazole (40 mg daily; n = 20) versus ranitidine (150 mg twice daily; n=18). Healing was proven endoscopically and patients were interviewed for dysphagia relief. Patients were assessed for relapse by endoscopy 6 months later. The follow-up period was a further 6 months. Patients received maintenance treatment with 40 mg omeprazole daily or ranitidine 150 mg twice daily and the total duration of treatment was 1 year. At 6 months, omeprazole produced a highly significant (P < 0.0001) greater rate of oesophagitis healing and highly significant (P < 0.0001) fewer dilatations compared with H₂-receptor antagonists (18 (90%) patients vs five (28%) patients, respectively; 3.5 vs 9.0 dilatations/patient). At 12 months, not one of the 18 successfully treated patients from the omeprazole group had relapsed. The two remaining patients required further dilatation and 40 and 60 mg omeprazole daily for healing. In comparison, all patients on ranitidine had to undergo further bougienage. In conclusion, omeprazole is a safe and effective maintenance treatment for preventing relapse of complicated reflux oesophagitis.     

Lansoprazole in the treatment of gastrooesophageal reflux disease in childhood

BACKGROUND: Acid suppressive therapy is the mainstay of pharmacologic treatment of gastro-oesophageal reflux disease. Use of proton pump inhibitors in children is still limited and has only included omeprazole in a few controlled studies. AIM: To determine efficacy of lansoprazole, a relatively new proton pump inhibitor, on symptoms and oesophagitis in a group of children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists. The required dose of the drug for inhibiting gastric acidity was also determined. PATIENTS AND METHODS: A series of 35 children (median age: 7.6 years, range: 3-15) with oesophagitis refractory to H2 receptor antagonists received a 12-week therapeutic course with lansoprazole. Prior to the study children underwent symptomatic and endoscopic assessment, oesophageal manometry and 24-hour intragastric and intra-oesophageal pH test. The latter was repeated after one week of therapy while patients were on treatment in order to monitor the degree of acid suppression and adjust the dose of the drug. Symptomatic assessment and endoscopy were repeated at the end of the trial RESULTS AND CONCLUSIONS: In 12 patients (group A), the initial dose of the drug was efficacious (1.3 to 1.5 mg/kg/day), whereas in 23 [group B) the initial dose (0.8 to 1.0 mg/kg/day) was increased by half because of insufficient inhibition of intragastric acidity (i.e., when the intra-gastric pH remained below 4.0 for more than 50% of the recording time). Nine patients in group A (75%) and 8 in group B (53.5%) healed (chi2: 3.6, p<0.05); 1 patient in group A [8.3%) and 7 in group B (30.5%) remained unchanged (chi2: 6.9, p<0.01); 2 patients in group A and 8 in group B improved and underwent a further month of therapy. The two groups did not differ as far as concerns baseline pH, endoscopic and clinical variables. In both groups, those patients failing to respond at the end of the trial showed a more impaired oesophageal motility than improved or healed patients. The drug was well tolerated and no significant laboratory abnormalities occurred. In children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists, a 12-week course of lansoprazole is effective both in healing oesophagitis and improving symptoms. An initial dose of 1.5 mg/kg/day of the drug is suggested. However, if during treatment, patients remain symptomatic the dose should be increased and a prolonged intra-gastric and intra-oesophageal pH test performed to evaluate the acid suppression efficacy of the adjusted dose. A short course of lansoprazole appears to be safe and well tolerated in paediatric age.     

Endoscopic Ultrasonographic Evaluation of Gastric Ulcer Healing on Treatment with Proton Pump Inhibitors versus H2-Receptor Antagonists

Tanaka M, Maruoka A. Chijiiwa Y, Tanaka M, Nawata H. Endoscopic ultrasonographic evaluation of gastric ulcer healing on treatment with proton pump inhibitors versus H₂-receptor antagonists. Scand J Gastroenterol 1994;29:1140-1144.

Background: It has been reported that time to peptic ulcer healing is shorter with proton pump inhibitors (PPI) than with H₂-receptor antagonists (H₂-RA). This study was designed to examine the difference in the healing process between gastric ulcers treated with PPI and those treated with H₂-RA.

Methods: The healing of deep gastric ulcers treated with PPI (n = 11) or H₂-RA (n = 13) was evaluated with endoscopic ultrasonography (EUS). Every 2 weeks during treatment EUS variables such as the width and the depth of the ulcer crater, the thickness and size of the low echoic area of the ulcer base, and the distance of the disrupted muscularis propria were measured. The contraction rates of EUS variables, the ratios of the contraction rate of the depth to that of the width of the ulcer crater (D/W ratio) and the contraction rate of the distance of the disrupted muscularis propria layer to that of the width of the ulcer crater (Dm/W ratio) were calculated.

Results: Only at week 2 were the D/W ratio and Dm/W ratio significantly higher in the group receiving PPI (D/W ratio, 1.79 ±0.701; Dm/W ratio, 0.938 ±0.207) than in the group receiving H₂-RA (D/W ratio, 1.10 + 0.559; Dm/W ratio, 0.641 ±0.166).

Conclusion: This study demonstrated that PPI therapy is associated with more rapid and stronger healing than obtained with H₂-RA during the early treatment period.     

Pharmacological and pharmacodynamic essentials of H(2)-receptor antagonists and proton pump inhibitors for the practising physician

The suppression of gastric acid secretion with anti-secretory agents has been the mainstay of medical treatment for patients with acid-related disorders. Although the majority of Helicobacter pylori -related peptic ulcers can be healed with antibiotics, ulcer healing and symptom control can be significantly improved when antibiotics are given with anti-secretory agents, especially with a proton pump inhibitor. There is a dynamic relationship between the suppression of intragastric acidity and the healing of peptic ulcer and erosive oesophagitis and control of acid-related symptoms. The suppression of gastric acid secretion achieved with H(2)-receptor antagonists has, however, proved to be suboptimal for effectively controlling acid-related disorders, especially for healing erosive oesophagitis and for the relief of reflux symptoms. H(2)-receptor antagonists are also not effective in inhibiting meal-stimulated acid secretion, which is required for managing patients with erosive oesophagitis. Furthermore, the rapid development of tolerance to H(2)-receptor antagonists and the rebound acid hypersecretion after the withdrawal of an H(2)-receptor antagonist further limit their clinical use. Although low-dose H(2)-receptor antagonists are currently available as over-the-counter medications for self-controlling acid-related symptoms, their pharmacology and pharmacodynamics have not been well studied, especially in the self-medicating population. Proton pump inhibitors have been proved to be very effective for suppressing intragastric acidity to all known stimuli, although variations exist in the rapidity of onset of action and the potency of acid inhibition after oral administration at the approved therapeutic doses, which may have important clinical implications for the treatment of gastro-oesophageal reflux disease and perhaps for eradicating H. pylori infection when a proton pump inhibitor is given with antibiotics. Once-daily dosing in the morning is more effective than dosing in the evening for all proton pump inhibitors with respect to the suppression of intragastric acidity and daytime gastric acid secretion in particular, which may result from a better bio-availability being achieved with the morning dose. When higher doses are needed, these drugs must be given twice daily to achieve the optimal suppression of 24 hour intragastric acidity. Preliminary results have shown that esomeprazole, the optical isomer of omeprazole, given at 40 mg, is significantly more effective than omeprazole 40 mg, lansoprazole 30 mg or pantoprazole 40 mg for suppressing gastric acid secretion. However, more studies in different patient populations are needed to compare esomeprazole with the existing proton pump inhibitors with regard to their efficacy, cost-effectiveness and long-term safety for the management of acid-related disorders.     

Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion

BACKGROUND: Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly. AIMS: We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects. SUBJECTS: A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis. METHODS: The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test. RESULTS: H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis. CONCLUSION: In Japan, erosive reflux oesophagitis occurs most often in the absence of H pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.     

Gastric H+, K+-ATPase as a therapeutic target in peptic ulcer disease

The presence of unbuffered acid appears to be an essential contributory factor in the pathogenesis of peptic ulcer disease. Treatment has concentrated therefore on the reduction of acidity, and the last decade has seen the widespread and effective use of H₂ antagonists. They are, at low doses, more successful in improving the natural history of duodenal ulcer disease than of gastric or esophageal ulceration. The H₂ receptor plays a central role in activation of parietal cell acid secretion, and antagonists at this receptor block most (but not all) of the acid secretion due to even gastrinergic or muscarinic (vagal) stimulation. In hypergastrinemic states such as Zollinger-Ellison syndrome, or where acid secretion has to be inhibited by more than 20% over a 24-hr period, such as for treatment of esophagitis, NSAID damage, or gastric ulcers, the dose and frequency of administration of the currently available antagonists must be increased to achieve reliable therapy. This has led to a search for an alternative target for acid inhibitory drugs, such as the gastric acid pump, the H⁺,K⁺-ATPase. This article focuses on the function of this ATPase and suggests that inhibition of this pump will provide a more efficacious means of reduction of acid secretion by the stomach, hence improving and simplifying therapy of acid related diseases.This work was supported in part by grants from NIH and the USVA.     

Pattern of Acid Reflux in Patients with Reflux Esophagitis ‘Resistant’ to H2-Receptor Antagonists

Ambulatory 24-h esophageal pH monitoring was carried out in 54 patients with erosive/ulcerative reflux esophagitis before a 12- to 24-week treatment with either ranitidine, 150 to 300 mg twice daily, or famotidine, 20 to 40 mg twice daily. After this period, 21 patients continued to present endoscopic evidence of esophagitis. Patients who did not respond to the therapy showed a more severe pretreatment pattern of acid reflux than those who healed, with regard to both median percentage time of reflux (16.2% versus 11.0%, respectively, p < 0.05) and median number of reflux episodes (88.0 versus 55.0; p < 0.05). Ambulatory 24-h esophageal pH-metry is therefore to be recommended in all patients with acid reflux symptoms, even in those who already show endoscopic lesions of the esophageal mucosa, since this test is a valid prognostic indicator of response to treatment.     

Omeprazole 10 Milligrams Once Daily,Omeprazole 20 Milligrams Once Daily,or Ranitidine 150 Milligrams Twice Daily,Evaluated as Initial Therapy for the Relief of Symptoms of Gastro-oesophageal Reflux Disease in General Practice

Background: The efficacy of omeprazole, 20 mg once daily, in the treatment of reflux oesophagitis and the therapeutic advantages over the histamine H₂ receptor antagonists are well documented. This study assessed 20 mg omeprazole daily (OM20), 10 mg omeprazole daily (OM10), and 150 mg ranitidine (RAN) twice daily for symptom relief in gastro-oesophageal reflux disease (GORD). Methods: Patients (n = 994) presenting with heartburn to their general practitioner underwent endoscopy to exclude peptic ulcer disease and were randomized into a UK, multicentre, parallel-group, double-blind comparison of the three treatments for 4 weeks. Symptoms were assessed at clinic visits after 2 and 4 weeks. Results: Symptom relief after 4 weeks was achieved by 61 % (OM20), 49% (OM10), and 40% (RAN) patients (OM20 versus OM10, P < 0.0167; OM20 versus RAN, P < 0.0001; OM10 versus RAN, P < 0.01). Among the patients (32%) with erosive reflux oesophagitis, symptom relief was achieved in 79% (OM20), 48% (OM10), and 33% (RAN) (OM20 versus OM10, P < 0.0001; OM20 versus RAN, P < 0.0001; OM10 versus RAN, NS). Conclusion: Omeprazole, 20 mg, is the most effective initial therapy for relief of GORD symptoms.     

The Effect of Cisapride in Maintaining Symptomatic Remission in Patients with Gastro-Oesophageal Reflux Disease

Background: Successful treatment of gastro-oesophageal reflux disease (GORD) has traditionally been assessed as healing of reflux oesophagitis, which may not be relevant in patients with moderate disease. In these patients symptom relief and patient satisfaction with therapy are of fundamental importance. Cisapride has well-documented prokinetic effects and may be well suited for long-term therapy of GORD, but its effectiveness in purely symptomatic treatment is unknown. We therefore compared two dosage regimens of cisapride with placebo over a period of 6 months in patients with evidence of gastro-oesophageal reflux, initially treated with antisecretory medication, with regard to maintaining symptom relief and satisfaction with treatment. Methods: Five hundred and thirty-five patients with reflux oesophagitis grade 1 (n = 293) or 2 (n = 124) or with no reflux oesophagitis but pathologic 24-h pH-metry (n = 118) achieved satisfactory symptom relief with an H₂-receptor antagonist or proton pump inhibitor within 4–8 weeks. In a double-blind randomized, parallel-group study, they were then treated with cisapride, 20 mg at night or 20 mg twice daily, or placebo and followed up for a maximum period of 6 months. Relapse was defined as dissatisfaction with therapy or an average consumption of more than two antacid tablets a day. Results: Median time to relapse was 63 days for cisapride, 20 mg twice daily; 59 days for cisapride, 20 mg at night; and 49 days for placebo. Time to relapse was not significantly different (P = 0.09). Presence and grade of oesophagitis at base line, type of therapy before randomization, and pattern of non-reflux symptoms at base line did not influence these findings significantly. Conclusion: The study indicates that cisapride is of limited value in maintenance therapy of GORD in patients in whom symptom relief has been accomplished with potent antisecretory medication. This ‘step-down’ approach to therapy seems disadvantageous in the long-term therapy of GORD.     

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.     

Gastroesophageal reflux disease

Opinion statement Lifestyle modifications should be discussed with every patient with symptoms of chronic gastroesophageal reflux disease (GERD). Proton pump inhibitors are the most efficacious medical therapy for GERD. H₂ receptor antagonists are likely to be effective in patients with mild to moderate GERD and for occasional symptoms. Promotility drugs have limited efficacy and produce frequent side effects. Surgery is a reasonable option for chronic management. Endoscopic therapy remains experimental until more long-term results are available.     

Acid and Pepsin Secretion in Patients with Esophagitis Refractory to Treatment with H2 Antagonists

The basis for treatment of esophagitis is suppression of gastric acid secretion. To determine whether lack of healing with standard treatment with H₂ antagonists might be due to abnormal gastric secretion, 30 patients who remained unhealed after 12 weeks' therapy with histamine H₂ antagonists were compared with 20 patients who healed after 6 or 12 weeks' therapy. The groups were matched with regard to age, weight, sex, and presence of hiatal hernia or duodenal ulcer. There were no significant differences in fasting gastric juice volume, pH, or acid or pepsin concentrations. All 30 refractory patients had basal acid output (BAO) <10 meq/h, and 16 of 30 had BAO <2 meq/h—that is, there was no evidence of hypersecretion in any refractory patients. Moreover, basal and maximal acid and pepsin outputs were not higher in non-healing patients. Refractory patients had a higher prevalence of initial severe (grade 3 or 4) esophagitis (80% versus 35% in those who healed, p < 0.01) and of strictures (73 versus 15%, p < 0.001), both of which serve as markers for refractoriness to treatment. Thus 77% of patients who presented with severe esophagitis failed to heal versus 32% of those with mild or moderate esophagitis (p < 0.01). Refractoriness of esophagitis is not related to gastric acid or pepsin hypersecretion but represents a constitutional susceptibility to esophagitis and requires both short- and long-term treatment strategies that are not yet well defined.     

Helicobacter pylori infection influences symptomatic response to anti-secretory therapy in patients with GORD—crossover comparative study with famotidine and low-dose lansoprazole

BACKGROUND AND AIM: Helicobacter pylori infection was reported to affect gastric acid secretion. We investigated the heartburn symptoms of patients with gastro-oesophageal reflux disease during sequential treatment with 40 mg of famotidine or 15 mg of lansoprazole to clarify whether H. pylori infection influences symptomatic response to anti-secretory therapy. SUBJECTS AND METHODS: The subjects were 33 gastro-oesophageal reflux disease patients, who had already been treated with a full dose of H2 receptor antagonist. First, famotidine at 20 mg b.i.d. was administered to the patients for 8 weeks. Second, famotidine was replaced with 15 mg of lansoprazole once in the morning for 8 weeks. Finally, 20 mg of famotidine was administered b.i.d. for 8 weeks instead of lansoprazole. Gastro-oesophageal reflux disease symptoms were assessed using an original visual analogue scale. RESULTS: The sequential symptomatic responses to famotidine and lansoprazole administration indicated that gastro-oesophageal reflux disease symptoms of patients during low-dose lansoprazole treatment were significantly less than those during famotidine treatment. Remission of symptoms was obtained significantly more often by famotidine therapy in patients with H. pylori infection than in patients without H. pylori infection. CONCLUSION: Low-dose lansoprazole is more effective than full-dose famotidine for the control of symptoms in patients with gastro-oesophageal reflux disease, and H. pylori infection influences the symptomatic response to H2 receptor antagonists.     

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.     

REVIEW: Efficacy of Rabeprazole Once Daily for Acid-Related Disorders

Proton-pump inhibitors (PPIs) have revolutionized the treatment of gastroesophageal reflux disease (GERD) and peptic ulcer. To evaluate the efficacy of the new PPI rabeprazole, 12 controlled clinical trials were conducted worldwide—three for each indication (erosive or ulcerative GERD healing, long-term GERD healing maintenance, duodenal ulcer healing, and gastric ulcer healing). Rabeprazole was compared to placebo, the H₂-receptor antagonist ranitidine, and the PPI omeprazole. Treatment duration ranged from 4 weeks for duodenal ulcer to 6 weeks for gastric ulcer, 8 weeks for GERD healing, and 1 year for maintenance of GERD healing. Rabeprazole was as effective as omeprazole for each indication and significantly more effective than ranitidine for healing of GERD (87% vs 66%) and duodenal ulcer (83% vs 73%). Rabeprazole was also superior to ranitidine in providing symptom relief, particularly in GERD.     

Low bedtime doses of H2-receptor antagonists for acute treatment of duodenal ulcer

Twenty-four-hour intragastric acidity was measured continuously over five separate occasions in 15 patients with healed duodenal ulcers. They were randomized to receive either placebo, cimetidine 800 mg, ranitidine 150 mg, famotidine 20 mg, or nizatidine 150 mg, given at 2200 hr in doubleblind fashion. All H₂-receptor blockers were more effective than placebo in suppressing both circadian (P<0.05–P<0.01) and nocturnal (P<0.002) gastric acidity, while there was no significant difference between the effects of the four active drugs in the same time periods. The percentage of nocturnal acid inhibition (2300–0800 hr) over placebo in terms of H⁺ values was virtually 100% with all active treatments. The effect on daytime (0800–1700 hr) and evening (1700–2300 hr) acidity of both placebo and the four H₂-receptor antagonists was similar. Therefore, in the above doses, H₂-receptor blockers guarantee overnight anacidity to a similar degree and cause the physiological buffering of daily meals on gastric acidity to be fully exploited. Furthermore, the reducing effect of daily meals on drug action can be prevented. Since strong acid suppression strictly confined to the nocturnal period has been shown to be closely correlated with the highest ulcer healing rates, it is suggested that single low bedtime doses of H₂-receptor antagonists should be evaluated in the acute treatment of duodenal ulcer.This study was supported in part by CNR grant 86.02120.03 and by CARIGE grant 104819/12.     

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole

BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.     

Short and long-term effect of two different dosages of ranitidine in the therapy of reflux oesophagitis

Many clinical trials on the effects of H2-antagonist drugs on reflux oesophagitis have shown unsatisfactory healing rates after conventional therapy, i.e. 4 to 12-week administration of 400 or 150mg bd of cimetidine or ranitidine, respectively. In order to verify if longer periods of treatment and/or higher dosage of drug can increase the healing rate, we performed a single-center double blind trial of 12 to 24 week duration on 75 patients with erosive/ulcerative reflux oesophagitis, comparing two ranitidine regimens, 150 vs 300mg bd. Patients who were healed after this period entered a 12 month maintenance treatment with half the dose previously received, i.e. 150 vs 300mg at bedtime. Our results show that, with both dosages, prolongation of acute treatment from 12 to 24 weeks allows complete additional healing of almost one fourth of patients. Furthermore, the data show that, both in the short and long-term treatment of reflux oesophagitis, conventional doses of ranitidine are as effective as double doses.     

Treatment of uncomplicated reflux disease

Uncomplicated reflux disease comprises the non-erosive reflux disease (NERD) and erosive reflux disease (ERD). The objectives of treatment are the adequate control of symptoms with restoration of quality of life, healing of lesions and prevention of relapse. Treatment of NERD consists in the administration of proton pump inhibitors (PPI) for 2-4 wk, although patients with NERD show an overall poorer response to PPI treatment than patients with ERD owing to the fact that patients with NERD do not form a pathophysiologically homogenous group. For long-term management on-demand treatment with a PPI is probably the best option. In patients with ERD, therapy with a standard dose PPI for 4-8 wk is always recommended. Long-term treatment of ERD is applied either intermittently or as continuous maintenance treatment with an attempt to reduce the daily dosage of the PPI (step-down principle). In selected patients requiring long-term PPI treatment, antireflux surgery is an alternative option. In patients with troublesome reflux symptoms and without alarming features empirical PPI therapy is another option for initial management. Therapy should be withdrawn after initial success. In the case of relapse, the long-term care depends on a careful risk assessment and the response to PPI therapy.