Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine.

Abstract

Objective-To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients.Design-Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks.Setting-Multicentre outpatient study at secondary referral centres in five European countries.Patients-297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal antiinflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial.Interventions-Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal antiinflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator's discretion.End point-Frequency of gastric and duodenal ulceration or lesions, or both.Measurements and main results-The cumulative incidence of peptic ulceration by eight weeks was 10-3% (27/263); 2 out of 135 (1-5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency ofgastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by four weeks, this difference was not evident by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection.Conclusions-Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.

An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs

“…52 Moreover, the protective effect of histamine H 2-blockers seen in RCTs have not translated well into clinical use. 52,53 For example, a recent study shows that using histamine H 2-blockers to suppress tNSAID-induced dyspepsia can double the risks of serious gastrointestinal bleeding. 51 However, this was an observational cohort study and there may be other confounding factors responsible for the gastrointestinal effects.…”

“…50,51 Histamine H2-blockers decrease the incidence of dyspepsia in patients using tNSAIDs, but at standard doses they appear to have little or no effect on the gastric lesions. 52 Moreover, the protective effect of histamine H 2-blockers seen in RCTs have not translated well into clinical use. 52,53 For example, a recent study shows that using histamine H 2-blockers to suppress tNSAID-induced dyspepsia can double the risks of serious gastrointestinal bleeding.…”

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling

“…Three studies recruited participants with Lanza scores of zero (undamaged GI surfaces). 48,49,57 One study only recruited patients with normal gastric mucosa. 46 One study recruited people with no more than one or two erosions or haemorrhages.…”

‘Guidelines’ or marketing for non‐steroidal anti‐inflammatory drug and proton pump inhibitor use?

“…(which parenthetically had repeatedly been shown to be ineffective for NSAID ulcer prevention) 4 and to half-dose misoprostol (200 lg b.d.) (equivalent to approximately 600 mg of cimetidine as an antisecretory drug).…”

“…We also found it ironic that Dr Graham suggested that industry support indicates that we were 'willing, trusting, and possibly naïve' tools of the study's sponsor. Review of Dr Graham's publications in the past 2 years reveals four articles assessing medications 1-3 or a diagnostic test 4 for which support was provided by the manufacturer of the product. Most articles published as guidelines, even those of the US national GI organizations, are not properly developed guidelines, but rather reviews by an author or authors who then make recommendations based on the results of their review.…”