Lower gastrointestinal events in a double-blind trial of the cyclo-oxygenase-2 selective inhibitor etoricoxib and the traditional nonsteroidal anti-inflammatory drug diclofenac.
OBJECTIVE
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause lower gastrointestinal (GI) clinical events such as bleeding. Cyclo-oxygenase (COX)-2 selective inhibitors decrease upper GI events, but no prospective trial has prespecified assessment of lower GI clinical events.


METHODS
Patients >or=50 years old with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 or 90 mg qd) or diclofenac (150 mg qd). Lower GI clinical events, confirmed by a blinded adjudication committee, included perforation or obstruction requiring hospitalization or bleeding (gross or occult rectal bleeding without upper GI cause associated with hypotension, orthostatic changes in heart rate [>20 beats per minute] or blood pressure [>20 mmHg systolic or >10 mmHg diastolic], hemoglobin drop >or=2 g/dl, or transfusion; or observed active bleeding or stigmata of hemorrhage).


RESULTS
We enrolled 34,701 patients with mean duration of therapy of 18 months. Rates were 0.32 and 0.38 lower GI clinical events per 100 patient-years for etoricoxib and diclofenac (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.63-1.13). Bleeding was the most common event (rates of 0.19 and 0.23 per 100 patient-years, respectively). Multivariable analysis revealed significant risk factors to be prior lower GI event (HR = 4.06; 95% CI, 2.93-5.62) and age >or=65 years (HR = 1.98; 95% CI, 1.45-2.71).


CONCLUSIONS
A statistically significant decrease in lower GI clinical events was not seen with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. The risk of a lower GI clinical event with NSAID use seems to be constant over time, and the major risk factors are a prior lower GI event and older age.
Laine
Loren
L
Division of Gastrointestinal & Liver Diseases, University of Southern California, Keck School of Medicine, Los Angeles, California, USA. llaine@usc.edu
Curtis
Sean P
SP
Langman
Michael
M
Jensen
Dennis M
DM
Cryer
Byron
B
Kaur
Amarjot
A
Cannon
Christopher P
CP
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D016001:Confidence Intervals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004008:Diclofenac / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000077613:Etoricoxib; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010003:Osteoarthritis / Q000188:drug therapy*; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D013450:Sulfones; D004008:Diclofenac; D000077613:Etoricoxib