Risks of clinically significant upper gastrointestinal events with etodolac and naproxen: a historical cohort analysis.
OBJECTIVE
Etodolac is a generic nonsteroidal anti-inflammatory drug (NSAID). Previous in vitro studies have shown that etodolac is a selective inhibitor of cyclooxygenase (COX)-2 with selectivity in between that of other COX-2 inhibitors such as celecoxib and rofecoxib. However, there are no outcomes data assessing clinically significant upper gastrointestinal (CSUGI) events with etodolac.


METHODS
A historical cohort study was performed at the Dallas Veterans Affairs Medical Center in which 16,286 veteran patients (5596 patient-years) received etodolac or naproxen during a 3-year period without concurrent use of other ulcerogenic drugs other than low-dose aspirin. The primary outcome was the CSUGI event rate of the etodolac and naproxen groups without concomitant low-dose aspirin.


RESULTS
The incidence of CSUGI events was .78% and .24% for naproxen and etodolac, respectively. In the NSAID-naive subset, the incidence of CSUGI events was .99% and .24% for naproxen and etodolac, respectively. Compared with naproxen, etodolac was associated with a reduction in upper gastrointestinal events, corresponding to an odds ratio of .39 (95% confidence interval, .20-.76; P = .006). Concomitantly used low-dose aspirin increased event rates with naproxen 2-fold and etodolac 9-fold. Hence, there was no significant difference in gastrointestinal event rates between etodolac and naproxen when low-dose aspirin was taken concomitantly.


CONCLUSIONS
Etodolac is a generic COX-2 selective inhibitor that reduces CSUGI events compared with the nonselective NSAID naproxen. However, concomitant use of low-dose aspirin negates the gastrointestinal safety advantages of etodolac.
Weideman
Rick A
RA
Department of Pharmacy, Dallas Veterans Affairs Medical Center, Dallas, TX 75216, USA.
Kelly
Kevin C
KC
Kazi
Salahuddin
S
Cung
Anh
A
Roberts
Kevin W
KW
Smith
Herbert J
HJ
Sarosi
George A
GA
Little
Bertis B
BB
Cryer
Byron
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D015331:Cohort Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D017308:Etodolac / Q000627:therapeutic use*; D005260:Female; D005767:Gastrointestinal Diseases / Q000145:classification / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D017308:Etodolac; D009288:Naproxen; D001241:Aspirin