Rates of Serious Gastrointestinal Events from Low Dose Use of Acetylsalicylic Acid, Acetaminophen, and Ibuprofen in Patients with Osteoarthritis and Rheumatoid Arthritis

JAMES F. FRIES and BONNIE BRUCE

ABSTRACT.

Objective. The frequency of serious gastrointestinal (GI) complications has been quantitated with chronic high doses of nonsteroidal antiinflammatory drugs (NSAID), but risk at lower dosages remains unknown. We examined the prevalence of serious GI events in patients taking aspirin (ASA), acetaminophen (APAP), or ibuprofen (IBU), focusing on low or intermittent use.

Methods. We studied 5692 patients with rheumatoid arthritis (RA) and 3124 patients with osteoarthritis (OA) from 12 databank centers, with 36,262 patient-years of observation, who had taken one of 3 study analgesics, and examined the frequency of serious GI events requiring hospitalization.

Results. Treatment groups were of similar ages and severity. As lower doses of study analgesics were taken, serious GI events tended to be less prevalent. In patients taking a study drug alone, without other analgesics or corticosteroids, only one event occurred in over 900 patient-years of exposure, roughly equivalent to background. Rates of GI events while taking APAP with other concurrent therapy or corticosteroids were higher (p < 0.05) than for the other 2 analgesics. In over-the-counter (OTC) doses, there were no significant differences in GI toxicity among analgesics. RA patients tended to have higher rates than OA patients. The rate of GI events was highly dependent on concurrent therapy, increasing 2 to 6-fold in patients taking other analgesics or corticosteroids. Propensity scores for serious GI events were similar across drugs.

Conclusion. OTC use of ASA, IBU, or APAP carries little risk of serious GI toxicity for most persons. Most serious problems encountered were in higher-risk patients. Given the low rates of events, at low or intermittent dosage without concurrent treatment, these 3 analgesics cannot be distinguished from each other or from background rates of serious GI toxicity. (J Rheumatol 2003;30:2226-33)

Key Indexing Terms:

NONSTEROIDAL ANTIINFLAMMATORY DRUG
GASTROPATHY
ASPIRIN
IBUPROFEN
ACETAMINOPHEN
GASTROINTESTINAL TOXICITY

---

From the Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.

Supported in part by a grant from the National Institutes of Health to ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), grant AR3584-05; and in part from a grant from Bayer Corporation.

J.F. Fries, MD; B. Bruce, DrPH, MPH, RD.

Address reprint requests to Dr. J.F. Fries, 1000 Welch Road, Suite 203, Palo Alto, CA 94304.

Submitted May 6, 2002; revision accepted March 28, 2003.

---