MISOPROSTOL REDUCES SERIOUS GASTROINTESTINAL COMPLICATIONS IN PATIENTS WITH RHEUMATOID-ARTHRITIS RECEIVING NONSTEROIDAL ANTIINFLAMMATORY DRUGS - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective: To investigate whether concurrent administration of misopro stol reduces the occurrence of serious upper gastrointestinal complica tions, such as perforation, gastric outlet obstruction, or bleeding, i n patients with rheumatoid arthritis who are receiving nonsteroidal an ti-inflammatory drugs (NSAIDs). Design: 6-month randomized, double-bli nd, placebo-controlled trial. Setting: 664 clinical practices of famil y medicine, internal medicine, or rheumatology in the United States an d Canada. Patients: 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symp toms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993. Intervention: Patients were randomly assigned to rec eive 200 mu g 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). Result s: Serious upper gastrointestinal complications were reduced by 40% (o dds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients r eceiving misoprostol (25 of 4404 patients) compared with those receivi ng placebo (42 of 4439 patients). During the first month, more patient s receiving misoprostol (20%) than placebo (15%) withdrew from the stu dy, primarily because of diarrhea and related problems (P < 0.001). Ri sk factors for serious upper gastrointestinal complications were incre asing age, history of peptic ulcer or bleeding, and cardiovascular dis ease. Patients with all four risk factors would have a 9% risk for a m ajor complication in 6 months. Conclusions: In older patients with rhe umatoid arthritis, misoprostol reduced serious NSAID-induced upper gas trointestinal complications by 40% compared with placebo.