Medline ® Abstracts for References 2-4
of 'NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity'
Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial.
Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, Geis GS
Ann Intern Med. 1995;123(4):241.
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 micrograms 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% CI, 0.364 to 0.982; P = 0.049]) 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<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.
University of Washington Medical School, Seattle 98195, USA.
Risk factors for serious nonsteroidal-induced gastrointestinal complications: regression analysis of the MUCOSA trial.
Simon LS, Hatoum HT, Bittman RM, Archambault WT, Polisson RP
Fam Med. 1996;28(3):204.
OBJECTIVES: This analysis evaluated the clinical and demographic risk factors for a suspected, serious nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complication in everyday clinical practice and calculated the risk reduction associated with misoprostol therapy in these "at-risk" patients.
METHODS: Using logistic regression analysis, the data set from a randomized, parallel, placebo-controlled trial of misoprostol in 8,843 rheumatoid arthritis patients taking NSAIDs (the Misoprostol Ulcer Complications Outcomes Safety Assessment trial) was modeled to identify risk factors for GI adverse events. The dependent variable was defined as a "suspected serious GI complication," and the independent variables included demographic features, level of functional disability, presence of co-morbid diseases, use of certain drugs, and treatment arm.
RESULTS: Two hundred forty-two suspected serious GI complications were observed; 102 occurred in the misoprostol treatment group (risk: 2.32%) and 140 in the placebo group (risk: 3.15%). Overall risk reduction due to misoprostol therapy was 26.6% (confidence interval 5.5%-42.9%, P<.05). However, in patient groups with identified risk factors, misoprostol use decreased the risk for an adverse GI event by 38.3%-87.3%. Specifically, those who benefitted significantly from therapy with misoprostol were patients with a history of peptic ulcer disease (risk reduction 52.4%), history of previous GI bleeding (risk reduction 50%), history of significant cardiovascular disease (risk reduction 38.3%), significant functional disability (risk reduction 87.2%), and patients whose symptoms required concomitant antacid use (risk reduction 48.3%).
CONCLUSION: We conclude that in everyday practice, patients who require chronic NSAID therapy and who have specific clinical risk factors may benefit from misoprostol co-therapy.
Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents.
Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, Johnson DA, Mahaffey KW, Quigley EM, Harrington RA, Bates ER, Bridges CR, Eisenberg MJ, Ferrari VA, Hlatky MA, Kaul S, Lindner JR, Moliterno DJ, Mukherjee D, Schofield RS, Rosenson RS, Stein JH, Weitz HH, Wesley DJ, American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents
J Am Coll Cardiol. 2008;52(18):1502.