Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use.
OBJECTIVE
Epidemiologic studies suggest nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk for lower gastrointestinal (GI) clinical events, but data from prospective trials are lacking. Cyclooxygenase (COX)-2-selective inhibitors decrease upper GI clinical events but the effect on lower GI events has not been determined. We performed a post hoc analysis of serious lower GI clinical events with a nonselective NSAID and a COX-2-selective agent in a prospective, double-blind, randomized GI outcomes trial.


METHODS
A total of 8076 rheumatoid arthritis patients 50 years or older (or 40 years or older on corticosteroid therapy) expected to require NSAIDs for 1 year or greater were randomly assigned to naproxen 500 mg twice daily or rofecoxib 50 mg daily. The rate of serious lower GI clinical events, defined as bleeding with a 2 g/dL drop in hemoglobin or hospitalization, or hospitalization for perforation, obstruction, ulceration, or diverticulitis, was determined.


RESULTS
The rate of serious lower GI events per 100 patient-years was 0.41 for rofecoxib and 0.89 for naproxen (relative risk, 0.46; 95% confidence interval [CI], 0.22-0.93; P = 0.032). Serious lower GI events accounted for 39.4% of all serious GI events (complicated upper GI event or lower GI event) among patients taking naproxen and 42.7% among those taking rofecoxib.


CONCLUSIONS
Serious lower GI events occurred at a rate of 0.9% per year in rheumatoid arthritis patients taking the nonselective NSAID naproxen, accounting for nearly 40% of the serious GI events that developed in these patients. Serious lower GI events were 54% lower with the use of the selective COX-2 inhibitor rofecoxib.
Laine
Loren
L
University of Southern California School of Medicine, Los Angeles 90033, USA. LLAINE@USC.EDU
Connors
Laurine G
LG
Reicin
Alise
A
Hawkey
Christopher J
CJ
Burgos-Vargas
Ruben
R
Schnitzer
Thomas J
TJ
Yu
Qinfen
Q
Bombardier
Claire
C
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects*; D011446:Prospective Studies; D011451:Prostaglandin-Endoperoxide Synthases; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases