. Objective : To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs). . Design : 6-month randomized, double-blind, placebo-controlled trial. . Setting : 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada. . Patients : 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993. . Intervention : Patients were randomly assigned to receive 200 μg of misoprostol or placebo four times a day. . Measurements : Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy). . Results : Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% Cl, 0.364 to 0.982 ; P = 0.0491) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P I 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months. . Conclusions : In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.

Misoprostol Reduces Serious Gastrointestinal Complications in Patients with Rheumatoid Arthritis Receiving Nonsteroidal Anti-Inflammatory Drugs: A Randomized, Double-Blind, Placebo-Controlled Trial

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)07273-2.pdf

Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.

Background Suppressing acid secretion is thought to reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain. Methods We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to double-blind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432 patients in whom treatment was successful to maintenance treatment with either 20 mg of omeprazole per day or 150 mg of ranitidine twice a day for six months. Results At eight weeks, treatment was successful in 80 percent (140 of 174) ...

A Comparison of Omeprazole with Ranitidine for Ulcers Associated with Nonsteroidal Antiinflammatory Drugs

The International Agency for Research on Cancer (IARC) was established in 1965 by the World Health Assembly, as an independently funded organisation within the framework of the World Health Organization. The headquarters of the Agency are in Lyon, France. The Agency conducts a programme of research concentrating particularly on the epidemiology of cancer and the study of potential carcinogens in the human environment. Its field studies are supplemented by biological and chemical research carried out in the Agency's laboratories in Lyon and, through collaborative research agreements, in national research institutions in many countries. The Agency also conducts a programme for the education and training of personnel for cancer research. The publications of the Agency contribute to the dissemination of authoritative information on different aspects of cancer research. Information about IARC publications, and how to order them, is available via the Internet at: http:// The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The authors alone are responsible for the views expressed in this publication.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.11334

IARC Handbooks of Cancer Prevention

Guidelines for prevention of NSAID-related ulcer complications

https://www.gastrojournal.org/article/0016-5085(91)90665-8/pdf

Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection.

Gastroduodenal intolerance is one of the major factors limiting the use of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatic diseases. We previously demonstrated that dyspepsia was not a marker for ulcer in NSAID users. We have now evaluated dyspeptic symptoms in 245 arthritic patients (receiving 13 different NSAIDs) from the practices of two rheumatologists. Fifty-seven patients (23%) gave a history of previous peptic ulcers. Heartburn, indigestion, or sour stomach at least once within the past year was present in 62.5%; 36.7% had experienced these symptoms within the previous 2 months and 28.6% within the previous week. Only 39 patients (15.9%) had experienced dyspepsia more than once daily within the previous month, and 8 (3.3%) had dyspepsia greater than 5 times/day. Thirty-four of the 39 patients with daily dyspepsia claimed to obtain relief with cimetidine or antacids (34 patients) or food (2 patients), whereas 3 had not discovered anything that provided relief. Women smokers were more likely than nonsmokers to experience dyspepsia (p less than 0.001). Neither men smokers nor those with a history of previous ulcer were more likely to have dyspepsia than nonsmokers or those without a history of ulcer (p greater than 0.5). We were not able to find a statistical association between any NSAID, or combination of NSAIDs, and the frequency of dyspepsia.

Sandra Lee Sessoms

Papers

Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection.

Dyspepsia in NSAID users: the size of the problem