Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial.
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).


METHODS
6-month randomized, double-blind, placebo-controlled trial.


METHODS
664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada.


METHODS
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.


METHODS
Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day.


METHODS
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.
Silverstein
F E
FE
University of Washington Medical School, Seattle 98195, USA.
Graham
D Y
DY
Senior
J R
JR
Davies
H W
HW
Struthers
B J
BJ
Bittman
R M
RM
Geis
G S
GS
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000627:therapeutic use*; D016017:Odds Ratio; D012307:Risk Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016595:Misoprostol